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51.
David Caba?ero Alyssa Baker Shengtai Zhou Gregory L Hargett Takeshi Irie Yan Xia Hélène Beaudry Louis Gendron Zara Melyan Susan M Carlton Jose A Morón 《Neuropsychopharmacology》2013,38(8):1472-1484
Withdrawal from prescribed opioids results in increased pain sensitivity, which prolongs the treatment. This pain sensitivity is attributed to neuroplastic changes that converge at the spinal cord dorsal horn. We have recently reported that repeated morphine administration triggers an insertion of GluA2-lacking (Ca2+-permeable) α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptors (AMPAR) in the hippocampus. This finding together with the reported involvement of AMPAR in the mechanisms underlying inflammatory pain led us to hypothesize a role for spinal AMPAR in opioid-induced pain behavior. Mice treated with escalating doses of morphine showed hypersensitivity to mechanical stimulation. Intrathecal administration of a Ca2+-permeable AMPAR selective blocker disrupted morphine-induced mechanical sensitivity. Analysis of the expression and phosphorylation levels of AMPAR subunits (GluA1/2/3/4) in homogenates and in postsynaptic density fractions from spinal cord dorsal horns showed an increase in GluA4 expression and phosphorylation in the postsynaptic density after morphine. Co-immunoprecipitation analyses suggested an increase in GluA4 homomers (Ca2+-permeable AMPAR) and immunohistochemical staining localized the increase in GluA4 levels in laminae III–V. The excitatory postsynaptic currents (EPSCs) recorded in laminae III–V showed enhanced sensitivity to Ca2+-permeable AMPAR blockers in morphine-treated mice. Furthermore, current–voltage relationships of AMPAR-mediated EPSCs showed that rectification index (an indicator of Ca2+-permeable AMPAR contribution) is increased in morphine-treated but not in saline-treated mice. These effects could be reversed by infusion of GluA4 antibody through patch pipette. This is the first direct evidence for a role of GluA4-containing AMPAR in morphine-induced pain and highlights spinal GluA4-containing AMPAR as targets to prevent the morphine-induced pain sensitivity. 相似文献
52.
Makoto Sugaya Kaoru Funamizu Michihiro Kono Yusuke Okuno Taisuke Kondo Ryusuke Ono Masashi Akiyama Chikako Nishigori Shinichi Sato 《The Journal of dermatology》2021,48(1):96-100
A case of xeroderma pigmentosum (XP) group D in a 39‐year‐old Japanese man is reported. The patient had suffered from moderate to severe solar sensitivity and freckle‐like pigmented macules in sun‐exposed areas since 6 years of age, and developed skin malignancies such as squamous cell carcinoma, actinic keratosis, Bowen’s disease and basal cell carcinoma. The minimal erythema dose for ultraviolet (UV) radiation was decreased with a delayed peak reaction. The level of unscheduled DNA synthesis of fibroblasts from the patient was 70% of normal, while they expressed POLH, a gene product responsible for the XP variant. Whole‐exome sequencing indicated that the patient harbored a homozygous mutation of c.1802G>T, p.Arg601Leu in ERCC2. A genetic complementation test was carried out by host cell reactivation assay, which showed that the patient’s fibroblasts recovered only when they were transfected with XPD cDNA, confirming the diagnosis of XP‐D. Arg601Leu mutation in ERCC2 may be related to mild UV radiation sensitivity and moderate skin lesions. 相似文献
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54.
Kosuke Nomura Toshiro Iizuka Daisuke Kaji Hisashi Yamamoto Yasutaka Kuribayashi Ryusuke Kimura Akihiro Yamada Tsukasa Furuhata Satoshi Yamashita Daisuke Kikuchi Akira Matsui Toshifumi Mitani Osamu Ogawa Shu Hoteya Yasunori Ota Shuichi Taniguchi Mitsuru Kaise 《Journal of gastroenterology and hepatology》2014,29(11):1867-1872
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56.
Ippei Ikushima Lene Jensen Anne Flint Tomoyuki Nishida Jeppe Zacho Shin Irie 《Advances in therapy》2018,35(4):531-544
Introduction
Semaglutide is a glucagon-like peptide-1 analogue for once-weekly subcutaneous treatment of type 2 diabetes. This trial compared the pharmacokinetics, pharmacodynamics, and safety of semaglutide in Japanese and Caucasian subjects.Methods
In this single-center, double-blind, parallel-group, 13-week trial, 44 healthy male subjects (22 Japanese, 22 Caucasian) were randomized within each race to semaglutide 0.5 mg (n = 8), 1.0 mg (n = 8), placebo 0.5 mg (n = 3) or 1.0 mg (n = 3). The primary endpoint was semaglutide exposure at steady state [area under the curve (AUC0–168h)].Results
Steady-state exposure of semaglutide was similar for both populations: AUC0–168h estimated race ratio (ERR), Japanese/Caucasian: 0.5 mg, 1.06; 1.0 mg, 0.99; maximum concentration (Cmax) ERR: 0.5 mg, 1.06; 1.0 mg, 1.02. Exposure after the first dose (0.25 mg) was slightly higher in Japanese versus Caucasian subjects (AUC0–168h ERR 1.11; Cmax ERR 1.14). Dose-dependent increases in AUC0–168h and Cmax occurred in both populations. Accumulation was as expected, based on the half-life (t1/2, ~ 1 week) and dosing interval of semaglutide. Significant body weight reductions were observed with semaglutide 0.5 mg and 1.0 mg in Japanese (both p ≤ 0.05) and Caucasian (both p ≤ 0.05) subjects versus placebo. No new safety issues were identified.Conclusions
The pharmacokinetic, pharmacodynamic, and safety profiles of semaglutide were similar in Japanese and Caucasian subjects, suggesting that no dose adjustment is required for the clinical use of semaglutide in Japanese subjects.Funding
Novo Nordisk A/S, Denmark.Trial registration
ClinicalTrials.gov identifier NCT02146079. Japanese trial registration number JapicCTI-142550.57.
Clinical Rheumatology - Janus kinase (JAK) inhibitors have been developed as disease-modifying antirheumatic drugs. Despite the positive therapeutic impacts of JAK inhibitors, concerns have been... 相似文献
58.
Takeshi Matsumoto Ryusuke Kusabiraki Akiko Arisawa Takahiro Fujiki Akihiro Noda Ayaka Tanaka Naoki Yamamoto Kensaku Aihara Shinpachi Yamaoka Michiaki Mishima 《Internal medicine (Tokyo, Japan)》2021,60(11):1785
Ethambutol-induced optic neuropathy (EON) is a well-known complication, although low-dose ethambutol seldom causes EON. An 85-year-old man with non-tuberculous mycobacterial lung disease was taking antibiotics, including low-dose ethambutol. On day 85 of treatment, the diagnosis of EON was made. Despite prior discontinuation, his best corrected visual acuity drastically deteriorated from 20/17 (right eye) and 20/20 (left eye) to 20/330 (right eye) and 20/1,000 (left eye) within 3 weeks, and this symptom did not resolve. To our knowledge, there have been no reported cases with drastically progressing and irreversible EON even after the withdrawal of low-dose and short-term ethambutol. 相似文献
59.
60.
Hiroshi Honda Tatsurou Fukuya Kuniyuki Kaneko Toshiro Kuroiwa Kengo Yoshimitsu Hiroyuki Irie Hitoshi Aibe Yuichi Ichiya Takashi Maeda Kenji Takenaka Kouji Masuda 《Journal of hepato-biliary-pancreatic sciences》1996,3(2):133-141
To determine the characteristic radiologic findings of inflammatory pseudotumor of the liver, various imagings of ten patients (11 lesions) with proven diagnoses of inflammatory pseudotumor were reviewed. Radiologic examinations, i.e., computed tomography (CT; 11 lesions), ultrasonography (11 lesions), magnetic resonance imaging (MRI; 6 lesions), angiography (10 lesions), CT during arterio-portography (CTAP; 3 lesions), and gallium-67 scans (9 lesions) were analyzed for their utility in diagnosis. No inflammatory pseudotumor showed a fibrous capsule around the lesion. Ten of the 11 lesions were poorly demarcated on most of the imagings, and all 11 lesions showed delayed and/or prolonged enhancement on CT or MRI. Arterio-portal shunting was observed in 4 lesions after contrast material administration on CT or angiography. Central lesions with suspiciously high fibrotic tissue content were demonstrated in 5 lesions on CT or MRI. Major vessels coursing in the lesions were demonstrated in 4 lesions by CT, MRI, and CTAP. Inflammatory pseudotumor of the liver should be included in the differential diagnosis in patients with hepatic masses, even if the patients are asymptomatic. If radiologic examinations suggest inflammatory pseudotumor, percutaneous biopsies should be performed so that unnecessary surgery can be avoided. 相似文献