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KITAHIRO YumiUniversity Hospital / Department of PharmacyAssistant Professor
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■ Award- Feb. 2026 第3回がんプロ研究シンポジウム, 優秀演題賞(メディカルスタッフ部門), ヒドロキシジンまたはベポタスチンの前投与によるリツキシマブ誘発 Infusion Reaction 発現抑制効果:多機関共同・⼆重盲検ランダム化⽐較第II相試験
- Jun. 2025 第33回医療薬学フォーラム, 優秀ポスター賞, リトドリン注射製剤による痒疹発現と原因物質の探索
- Mar. 2025 日本薬学会, 日本薬学会第145会年会学生優秀発表賞(ポスター発表の部), フルオロウラシルによるメラニン産生を抑制する化合物の探索
- Nov. 2024 日本医療薬学会, JPHCS 誌論文賞, Significance of pharmacist intervention to oral antithrombotic therapy in the pharmaceutical outpatient clinic of cardiovascular internal medicine: a retrospective cohort study
- Nov. 2023 日本医療薬学会, 第33回日本医療薬学会年会 優秀演題賞(International Session), Effect of early dose reduction of osimertinib on efficacy in the first-line treatment for EGFR-positive non-small cell lung cancer
- Jun. 2023 日本医療薬学会, 第6回フレッシャーズ・カンファランス優秀演題発表賞, 肺胞上皮細胞におけるエベロリムスの上皮間葉転換誘導とシグナル伝達因子の関連
- Mar. 2023 日本薬学会, 日本薬学会第143会年会学生優秀発表賞(ポスター発表の部), ユビキチンリガーゼHRD1を誘導する化合物の探索と神経細胞死抑制効果の検討
- Valganciclovir (VGCV) is the first-line drug for preemptive therapy of cytomegalovirus (CMV) infection. However, even at standard doses, plasma concentrations of the active metabolite ganciclovir (GCV) show substantial inter-individual variability. To ensure therapeutic efficacy and minimize adverse effects, therapeutic drug monitoring (TDM) based on the area under the concentration-time curve (AUC) is essential. Yet, conventional TDM via venous blood sampling is invasive and unsuitable for frequent monitoring. In this study, we aimed to develop a simple and minimally invasive method for GCV quantification using dried blood spots (DBS) combined with liquid chromatography-tandem mass spectrometry (LC-MS/MS). The method demonstrated a good linearity over a concentration range of 0.25-16 μg/mL and satisfied the validation criteria for accuracy and precision. It showed acceptable stability for up to 7 days under refrigerated conditions. Methanol was identified as the optimal extraction solvent, allowing for a simplified sample pretreatment without the need for ultrasonic processing. While hematocrit levels affected spot size and quantification accuracy, reliable measurements were obtained within the 30%-50% hematocrit range. The established DBS-based LC-MS/MS method provides a promising, minimally invasive approach for TDM of GCV in the management of CMV infections.Apr. 2026, Biomedical chromatography : BMC, 40(4) (4), e70411, English, International magazineScientific journal
- Feb. 2026, Journal of pharmaceutical health care and sciences, English, International magazine[Refereed]Scientific journal
- Lead, Jan. 2026, Journal of pharmaceutical health care and sciences, 12(14) (14), English, International magazine[Refereed]Scientific journal
- Bortezomib, a first-in-class proteasome inhibitor, is widely used to treat multiple myeloma and other hematological malignancies. Despite its therapeutic efficacy, bortezomib causes peripheral neuropathy (PN) in approximately 20-30% of patients, often leading to dose reduction or discontinuation. Preventive or therapeutic approaches to bortezomib-induced PN are currently unavailable, as its precise mechanism remains unclear. In this study, we compared the effects of bortezomib and the second-generation proteasome inhibitor carfilzomib on peripheral nerve cells to identify candidate molecules involved in PN development. Transcriptome profiling of differentiated F11 cells, a hybridoma of a rat embryonic dorsal root ganglion and mouse neuroblastoma cell line N18TG2, revealed that bortezomib selectively upregulated α/β-hydrolase containing domain 4 (Abhd4), whereas carfilzomib did not. This finding was confirmed by quantitative RT-PCR and immunoblotting, which demonstrated consistent increases in Abhd4 mRNA and protein levels following bortezomib treatment. Functional analysis further revealed that Abhd4 overexpression promoted early apoptosis, suggesting a mechanistic link between bortezomib-induced Abhd4 elevation and neuronal vulnerability. Therefore, these results suggest that Abhd4 represents a candidate molecular signature associated with bortezomib-induced PN. Although further in vivo validation is needed, these findings warrant further investigation of Abhd4 as a potential contributor to bortezomib-induced PN.2026, Biological & pharmaceutical bulletin, 49(3) (3), 496 - 502, English, Domestic magazine[Refereed]Scientific journal
- OBJECTIVE: Parkinson's disease (PD) is a neurodegenerative disorder characterized by the loss of dopaminergic neurons. Endoplasmic reticulum (ER) stress contributes to PD pathogenesis, with the ER-associated degradation (ERAD) system playing a protective role. HRD1, an ER-resident ubiquitin ligase, and its stabilizer SEL1L are involved in ERAD and neuronal survival. This study investigated alterations in the plasma levels of microRNA-101 (miR-101), which targets SEL1L, in patients with PD, and its potential role as a biomarker. RESULTS: Plasma miR-101 levels in patients with PD significantly decreased compared with those in healthy controls. Receiver operating characteristic curve analysis demonstrated that miR-101 could moderately discriminate patients with PD from healthy individuals (area under the curve = 0.781, 95% confidence interval = 0.547-1.00). The optimal cutoff, as determined by the Youden index, was 0.737 (expression ratio relative to that in the healthy control group), yielding a sensitivity of 50% and specificity of 100%. These results suggested that reduced plasma miR-101 expression may reflect the pathophysiological state of PD, and miR-101 has potential as minimally invasive biomarker for PD.Dec. 2025, BMC research notes, English, International magazine[Refereed]Scientific journal
- A survey, given before and after practical training, evaluated the educational effect of simulated role-playing (RP) on student awareness and knowledge of pregnancy and medication counselling. In the post-training survey responses, students recognized the importance of using specific numbers when explaining and counselling for medications. The students understood more of the challenges pharmacists face concerning specialized drug use for pregnant and breastfeeding women. The training did not result in a statistically significant change in the overall correct answer rate of knowledge-based questions regarding pregnancy and medications. However, the role-playing intervention increased the number of correct answers on questions related to the appropriate terminology used in medication counseling. In conclusion, the practical training with role-playing provided valuable education in developing professional pharmacist attitudes and meeting the competency requirements for counseling on pregnancy medications.Japan Society for Pharmaceutical Education, Dec. 2025, Japanese Journal of Pharmaceutical Education, 9, e09050, Japanese[Refereed]Scientific journal
- Reports on serum acyclovir (ACV) concentrations in patients undergoing continuous hemodiafiltration (CHDF) remain limited. We present a case describing the impact of CHDF on serum ACV levels in a patient with encephalopathy. A Japanese woman in her 70s was prescribed oral valacyclovir (VACV) at a dose of 1000 mg three times daily for herpes zoster ophthalmicus. After 7 days of treatment, she was admitted to a local hospital with fever, dysarthria, altered consciousness, hallucinations, and headache. Her serum creatinine level was elevated at 4.02 mg/dL. Intravenous ACV was initiated under the clinical suspicion of varicella zoster virus (VZV) encephalitis. However, after 3 days of treatment without improvement in consciousness, she was transferred to our hospital. Her serum ACV concentration upon admission was 14.1 μg/mL. Suspecting ACV-induced encephalopathy and renal dysfunction, CHDF was promptly initiated. Following CHDF therapy, serum ACV levels declined rapidly, accompanied by a gradual improvement in consciousness. This case suggests that CHDF may be an effective therapeutic option for managing ACV-associated nephropathy and encephalopathy.Nov. 2025, Journal of infection and chemotherapy : official journal of the Japan Society of Chemotherapy, 31(12) (12), 102859 - 102859, English, International magazine[Refereed]Scientific journal
- BACKGROUND: Despite its common use for analgesia in neonatal intensive care units, the optimal dosing and safety profile of fentanyl, particularly regarding suspected fentanyl-emerged adverse events (FEAEs), such as hypotension, desaturation, and oliguria, are not well-defined. OBJECTIVE: This study aimed to develop an optimal therapeutic monitoring and dosing strategy for fentanyl for neonates. A physiologically based pharmacokinetic (PBPK) model for predicting fentanyl pharmacokinetics across various populations, including preterm and term neonates, was developed, and the relationship between predicted fentanyl exposure and FEAE incidence in neonates was assessed. METHODS: A PBPK model was developed and validated against the observed values in the literature. The model's predictive accuracy for fentanyl pharmacokinetics and association with FEAE incidence in an external retrospective cohort of Japanese neonates was evaluated using the predicted concentrations and pharmacokinetic parameters estimated by PBPK simulation. RESULTS: The PBPK model exhibited reasonable predictive performance for serum fentanyl concentrations in actual neonatal patients (mean error: 9.27% [standard error: 5.06%], root mean squared error: 54.7%). The incidence of any FEAE, particularly oxygen desaturation, was associated with the fentanyl concentration-to-dose ratio, but not with some exposure parameters, such as the area under the curve and maximum concentration. The recommended reduced infusion rate allowed serum fentanyl concentrations to fall within the ranges established by the reported values and our data. CONCLUSIONS: Our PBPK model and proposed dosing strategy may contribute to safer and more effective fentanyl use in neonates.Sep. 2025, Clinical pharmacokinetics, English, International magazine[Refereed]Scientific journal
- PURPOSE: Infusion-related reaction (IRR) is a common adverse event induced by rituximab. Although first-generation histamine 1 receptor antagonists (H1RAs) are commonly used to prevent IRR, evidence on IRR suppression by the second-generation H1RA bepotastine is scarce. In this study, we assessed the inhibitory effects of bepotastine on rituximab-induced IRR and compared them with those of the first-generation H1RA diphenhydramine. METHODS: We retrospectively evaluated IRR incidence in patients with B-cell non-Hodgkin lymphoma who received their first dose of rituximab. RESULTS: The incidence of any grade IRR was 9.8% in the bepotastine group (n = 92), which was significantly lower than the 30.2% rate in the diphenhydramine group (n = 96; p < 0.001). The incidence of grade 2 or higher IRR was similar between the two groups (6.5% vs. 12.5%; p = 0.16). Multivariable logistic regression analysis revealed that the risk of any grade IRR incidence was higher in patients with B symptoms and bulky disease. Premedication with bepotastine was an independent factor in reducing the risk of any grade IRR incidence (odds ratio = 0.19, 95% confidence interval: 0.08-0.47). CONCLUSION: Bepotastine may be more effective than diphenhydramine in reducing the incidence of rituximab-induced IRR, particularly low-grade reactions.Sep. 2025, International journal of hematology, 122(3) (3), 413 - 420, English, Domestic magazine[Refereed]Scientific journal
- PURPOSE: Oral lichen planus (OLP) is a chronic, refractory type of stomatitis characterized by abnormal keratinization and often accompanied by pain. The best treatment for OLP, particularly for pain management, remains unclear. This study focuses on the short-term efficacy of ibuprofen gargle for pain relief in patients with OLP. METHODS: In this crossover study, 24 patients with painful OLP were enrolled. One group received an ibuprofen gargle (0.6%) on days one and three to five and a placebo on day two. The other group received a placebo on day one and ibuprofen on days two to five. The primary outcome was the change in pain level, measured by a Visual Analogue Scale (VAS) before and after gargling on days one and two. Additionally, changes in each domain of the Patient-Reported Oral Mucositis Symptom (PROMS) scale were evaluated from days one to five. RESULTS: There was no significant difference in the degree of reduction in pain VAS values between the ibuprofen and placebo groups before and five and 15 minutes after use of the gargle. However, the PROMS scale showed a significant reduction in dietary restrictions (p = 0.032) in favor of the ibuprofen gargle compared to baseline. CONCLUSION: Ibuprofen gargle may help alleviate dietary restrictions associated with oral intake in patients with OLP who experience pain. TRIAL REGISTRATION: This study was registered with the Japan Registry of Clinical Trials (jRCT) (jRCTs051220009).Aug. 2025, Cureus, 17(8) (8), e91242, English, International magazine[Refereed]Scientific journal
- BACKGROUND: Valganciclovir (VGCV) is administered at a dose of 16 mg/kg 2 times daily for 6 months to treat symptomatic congenital cytomegalovirus (CMV) infections. During the treatment period, approximately 20% of the patients developed grade 3 or higher neutropenia. Currently, information on the pharmacokinetics and pharmacodynamics of ganciclovir, an active metabolite of VGCV, in infants is limited. In the current study, the relationship between ganciclovir concentration and neutropenia was investigated, and a population pharmacokinetic (PPK) model of ganciclovir in infants with symptomatic congenital CMV infection was developed. METHODS: Japanese infants who were prescribed oral VGCV for symptomatic congenital CMV infections between July 2017 and January 2021 were included. The relationship between the observed trough ganciclovir concentrations and neutrophil counts was examined. PPK analysis was performed to evaluate the covariates affecting the pharmacokinetics of ganciclovir. RESULTS: Twenty-seven ganciclovir serum samples from 8 patients were analyzed. A moderate negative correlation was observed between the observed trough ganciclovir concentration and neutrophil count. PPK model analysis showed that postmenstrual age (PMA) affected the total body clearance of ganciclovir after correcting for the empirical allometric scaling of body weight. Based on PMA and body weight, a nomogram to achieve the target area under the concentration-time curve from 0 to 24 hours of 40-60 mcg·h·mL -1 of ganciclovir was calculated. CONCLUSIONS: The relationship between neutrophil count and ganciclovir trough concentration in infants was clarified. The PPK model showed that the dose of VGCV should be reduced in patients with a low PMA to achieve target exposure.Jun. 2025, Therapeutic drug monitoring, 47(3) (3), 393 - 399, English, International magazineScientific journal
- BACKGROUND: Torasemide, a loop diuretic, is rarely used for pregnant women because of the risk of reduced placental blood flow resulting from decreased circulating plasma volume. We experienced a case of a newborn with metabolic alkalosis and mild polyuria. The mother was suspected of self-medicating as we detected torasemide in the neonatal serum by LC-MS/MS method. CASE PRESENTATION: A Japanese pregnant woman in her 20s with mental illness, symptoms of panic and eating disorders, and a history of overdosing on over-the-counter medications, was referred to our hospital for birth control. She presented with vomiting following bulimia nervosa and hypokalemia. Her baby was delivered vaginally at 36 weeks and 4 days of gestation. The baby's blood gas analysis on day 0 revealed metabolic alkalosis (pH > 7.42, HCO3- > 28 mmHg). Up to 16 h after birth, mild polyuria and a urine output of 3.3 mL/kg/h were observed without the administration of diuretics. We suspected diuretic intake by the mother before delivery, because she had a history of taking torasemide before being referred to the hospital. As expected, torasemide was detected in the baby's serum. The serum concentration on the first day after delivery (4.80 ng/mL) gradually decreased to 0.45 ng/mL on day 5, whereas torasemide was not detected in the maternal serum. Neonatal metabolic alkalosis improved by day 3 following birth. CONCLUSIONS: This case suggests close counseling and monitoring of pregnant women before childbirth regarding their past and present use of drugs, particularly in those with mental illness.Apr. 2025, Journal of pharmaceutical health care and sciences, 11(31) (31), 1 - 5, English, International magazine[Refereed]Scientific journal
- Feb. 2025, JMIR Research Protocols[Refereed]Scientific journal
- A woman in her 70s who was taking warfarin 3.75 mg/day had a prothrombin time-international normalized ratio (PT-INR) within the therapeutic range. Her medication for pulmonary hypertension was changed from bosentan to macitentan. After 40 days, she developed respiratory distress, anorexia, and vomiting caused by common cold. When she visited the pharmaceutical outpatient clinic without reservation, the pharmacist suspected that bosentan discontinuation, which cancelled cytochrome P450 (CYP) 2C9 and CYP3A4 enzyme induction, and decreased vitamin K intake due to appetite loss had enhanced warfarin effect, causing PT-INR prolongation. The pharmacist requested the physician to examine the patient's PT-INR. Results showed that her PT-INR was >7. Hence, she was urgently hospitalized. Warfarin and macitentan were discontinued, and the patient's PT-INR decreased to 1.77 after the intravenous administration of vitamin K. Her appetite improved, and warfarin 2 mg/day was resumed. Additionally, when she had been administered macitentan, her hemoglobin levels decreased from 10.8 to 6.6 mg/dL. Therefore, the pharmacist and the physician during hospitalization planned to resume treatment with bosentan, but not with macitentan. The pharmacist proposed to increase the warfarin dose to 3.75 mg since the bosentan and warfarin interaction could lower PT-INR. Thereafter, the patient's PT-INR was controlled within the therapeutic range, and her hemoglobin level was 8-9 mg/dL. The patient was discharged on day 17 of admission. Thus, pharmacist intervention plays a significant role in warfarin control with consideration of drug-drug interaction in patients receiving pulmonary hypertension treatment.Feb. 2025, The Kobe journal of medical sciences, 70(4) (4), E125-E129, English, Domestic magazine[Refereed]Scientific journal
- BACKGROUND: Valganciclovir (VGCV) is administered at a dose of 16 mg/kg 2 times daily for 6 months to treat symptomatic congenital cytomegalovirus (CMV) infections. During the treatment period, approximately 20% of the patients developed grade 3 or higher neutropenia. Currently, information on the pharmacokinetics and pharmacodynamics of ganciclovir, an active metabolite of VGCV, in infants is limited. In the current study, the relationship between ganciclovir concentration and neutropenia was investigated, and a population pharmacokinetic (PPK) model of ganciclovir in infants with symptomatic congenital CMV infection was developed. METHODS: Japanese infants who were prescribed oral VGCV for symptomatic congenital CMV infections between July 2017 and January 2021 were included. The relationship between the observed trough ganciclovir concentrations and neutrophil counts was examined. PPK analysis was performed to evaluate the covariates affecting the pharmacokinetics of ganciclovir. RESULTS: Twenty-seven ganciclovir serum samples from 8 patients were analyzed. A moderate negative correlation was observed between the observed trough ganciclovir concentration and neutrophil count. PPK model analysis showed that postmenstrual age (PMA) affected the total body clearance of ganciclovir after correcting for the empirical allometric scaling of body weight. Based on PMA and body weight, a nomogram to achieve the target area under the concentration-time curve from 0 to 24 hours of 40-60 mcg·h·mL-1 of ganciclovir was calculated. CONCLUSIONS: The relationship between neutrophil count and ganciclovir trough concentration in infants was clarified. The PPK model showed that the dose of VGCV should be reduced in patients with a low PMA to achieve target exposure.Sep. 2024, Therapeutic drug monitoring, English, International magazine[Refereed]Scientific journal
- BACKGROUND: Brexpiprazole is a second-generation antipsychotic approved in Japan in 2018; however, information on placental passage and breast milk transfer remains limited. In this report, the patient, a 30-year-old pregnant woman with schizophrenia, was medicated with brexpiprazole, risperidone, and quetiapine. METHODS: The study used high-performance liquid chromatography-tandem mass spectrometry to determine the concentrations of brexpiprazole, quetiapine, risperidone, and its active metabolite (paliperidone) in maternal and neonatal plasma, cord venous plasma, and breast milk. Maternal plasma samples were obtained approximately 2 and 8 hours after the last administration of antipsychotics on the day of delivery and at the estimated drugs' trough time on days 1, 3, and 5 after delivery. RESULTS: The maternal plasma concentrations of brexpiprazole, quetiapine, and paliperidone increased by approximately 3.5-fold on the fifth day compared with those on the day of delivery, whereas the risperidone concentration remained almost constant. Moreover, the neonatal plasma concentrations of the 4 drugs immediately after birth were indistinguishable from the umbilical cord concentrations and gradually decreased, except for risperidone. Relative infant doses of these compounds were below 1.1%. CONCLUSIONS: Pregnancy status notably alters the pharmacokinetic properties of antipsychotics. Therefore, close and careful monitoring of clinical symptoms should be considered during pregnancy and after delivery. Although brexpiprazole is transferred to neonates through the placenta, breastfeeding is still possible because the relative infant dose value of this drug was much less than 10%.Apr. 2024, Therapeutic drug monitoring, English, International magazine[Refereed]Scientific journal
- Elsevier BV, Mar. 2024, Drug Metabolism and Pharmacokinetics, 101009 - 101009[Refereed]Scientific journal
- BACKGROUND: Rituximab, an anti-CD20 monoclonal antibody, can cause infusion reactions (IRs), especially during the initial rituximab infusion therapy. Generally, patients are administered a histamine H1-receptor antagonist before the rituximab infusion, along with an antipyretic analgesic, to prevent or reduce IRs. Multiple retrospective case-control studies indicate that the second generation of histamine H1-receptor antagonists might be more effective than the first generation in suppressing IRs caused by the rituximab infusion. OBJECTIVE: This study aimed to assess the efficacy of first- and second-generation histamine H1-receptor antagonists for preventing IRs resulting from the initial infusion of rituximab in patients diagnosed with non-Hodgkin lymphoma. METHODS: This is a phase II, double-blind, active-controlled randomized trial. It will be a multicenter study conducted across 3 facilities that aims to enroll a total of 40 patients diagnosed with non-Hodgkin lymphoma who will receive their initial rituximab infusion. Participating patients will be administered hydroxyzine pamoate or bepotastine besilate, representing first- or second-generation histamine H1-receptor antagonists, respectively. This will be combined with 400-mg acetaminophen tablets taken approximately 30 minutes before the first infusion of rituximab. The primary end point of this trial is to assess severe IRs, equivalent to grade 2 or higher as defined by the National Cancer Institute Common Terminology Criteria for Adverse Events, version 5.0, that occur within a 4-hour period after the initiation of rituximab infusion. The secondary end points include assessing the severity of the initial IR, the maximum severity of the IR, and the duration between rituximab infusion initiation and the onset of the first IR within a 4-hour period. Additionally, the trial will evaluate histamine H1-receptor antagonist-induced drowsiness using the visual analogue scale, with each patient providing their individual response. RESULTS: This study began with patient recruitment in April 2023, with 17 participants enrolled as of November 12, 2023. The anticipated study completion is set for February 2026. CONCLUSIONS: This study is the first randomized controlled trial comparing the effects of oral first- and second-generation histamine H1-receptor antagonists in preventing IRs induced by the initial administration of rituximab. The findings from this study hold the potential to establish the rationale for a phase III study aimed at determining the standard premedication protocol for rituximab infusion. TRIAL REGISTRATION: Japan Registry of Clinical Trials jRCTs051220169; https://jrct.niph.go.jp/latest-detail/jRCTs051220169. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/54882.Lead, Feb. 2024, JMIR research protocols, 13, e54882, English, International magazine[Refereed]Scientific journal
- Dec. 2023, Drug Metabolism and Pharmacokinetics[Refereed]Scientific journal
- BACKGROUND: Optimised antithrombotic therapy requires clinical experience and an understanding of the current guidelines. This retrospective study aimed to evaluate whether pharmacist interviews and interventions with patients taking oral antithrombotic drugs in the pharmaceutical outpatient cardiology clinic had favourable clinical outcomes including decreased bleeding. METHODS: The participants included patients visiting the outpatient clinic of cardiovascular internal medicine at the Kobe University Hospital from January-December 2017, and were taking oral antithrombotic medication. The observation period was from the first visit to the outpatient clinic to October 2021 or death. Patients who received pharmacist intervention more than twice were defined as the pharmacist intervention group. Two control patients per one pharmacist intervention group individual were selected from the non-intervention pool matched for age, gender and antithrombotic medication type. RESULTS: Of the 895 eligible patients, 132 were in the pharmacist intervention group and 264 were selected for the matched non-intervention group. Bleeding events according to the Bleeding Academic Research Consortium criteria over type 2 were significantly lower in the pharmacist intervention group compared with the non-intervention group (17.4% versus 28.4%, P = 0.019). There were no significant differences in mortality and heart failure hospitalisation frequency, stroke, or cardiovascular events between the groups. Multivariate analysis identified age (≥ 65 years) and pharmacist intervention as factors associated with bleeding (odds ratio = 2.29 and 0.51, respectively). CONCLUSION: Pharmacist intervention in the outpatient clinic of cardiovascular internal medicine was effective in reducing the risk of bleeding in patients undergoing antithrombotic therapy.Sep. 2023, Journal of pharmaceutical health care and sciences, 9(1) (1), 28 - 28, English, International magazine[Refereed]Scientific journal
- Parkinson's Disease (PD) is caused by many factors and endoplasmic reticulum (ER) stress is considered as one of the responsible factors for it. ER stress induces the activation of the ubiquitin-proteasome system to degrade unfolded proteins and suppress cell death. The ubiquitin ligase 3-hydroxy-3-methylglutaryl-coenzyme A reductase degradation 1 (HRD1) and its stabilizing molecule, the suppressor/enhancer lin-12-like (SEL1L), can suppress the ER stress via the ubiquitin-proteasome system, and that HRD1 can also suppress cell death in familial and nonfamilial PD models. These findings indicate that HRD1 and SEL1L might be key proteins for the treatment of PD. Our study aimed to identify the compounds with the effects of upregulating the HRD1 expression and suppressing neuronal cell death in a 6-hydroxydopamine (6-OHDA)-induced cellular PD model. Our screening by the Drug Gene Budger, a drug repositioning tool, identified luteolin as a candidate compound for the desired modulation of the HRD1 expression. Subsequently, we confirmed that low concentrations of luteolin did not show cytotoxicity in SH-SY5Y cells, and used these low concentrations in the subsequent experiments. Next, we demonsrated that luteolin increased HRD1 and SEL1L mRNA levels and protein expressions. Furthermore, luteolin inhibited 6-OHDA-induced cell death and suppressed ER stress response caused by exposure to 6-OHDA. Finally, luteolin did not reppress 6-OHDA-induced cell death when expression of HRD1 or SEL1L was suppressed by RNA interference. These findings suggest that luteolin might be a novel therapeutic agent for PD due to its ability to suppress ER stress through the activation of HRD1 and SEL1L.Aug. 2023, Neurochemical research, English, International magazine[Refereed]Scientific journal
- Oral lichen planus (OLP) is a type of chronic and refractory stomatitis characterized by abnormal keratinization, which is often painful. There is no consensus regarding treatment options for OLP, particularly in the presence of pain. The current study protocol focuses on the short-term efficacy and long-term safety of an ibuprofen gargle for pain management in patients with OLP. Patients (n = 24) with painful OLP will be enrolled. During a crossover study period, patients in the ibuprofen–placebo (IP) group will receive an ibuprofen gargle (0.6%) on day 1, a placebo gargle on day 2, and an ibuprofen gargle on days 3–5 at least once daily. Patients in the placebo–ibuprofen (PI) group will receive a placebo gargle on day 1, an ibuprofen gargle on day 2, and an ibuprofen gargle on days 3–5 at least once daily. The primary endpoint of the crossover study period is the change in pain level as measured by a visual analogue scale score from before gargle administration to 5 min after gargle administration on days 1 and 2. The primary endpoint of the long-term extension study is assessment of long-term safety. The results of this study may support existing evidence regarding the effectiveness of ibuprofen rinses in treating OLP.Lead, MDPI AG, Jan. 2023, Methods and Protocols, 6(1) (1), 7 - 7, English, International magazine[Refereed]Scientific journal
- Dried achene or anthocarpous accessory fruits of Rosa multiflora Thunb., Rosae fructus ("Eijitsu" in Japanese), have been used in clinical practice to improve constipation within traditional Japanese medicine. Recently, it has been claimed that the efficacy of this crude drug is decreasing, and multiflorin A, the purgative component, was not detected within the tested samples. In order to clarify the causes of this issue, we investigated Rosa section Synstylae (Rosaceae), including R. multiflora, growing in Japan and South Korea with a focus on the secondary metabolite, multiflorin A. We recognize that there are two chemotypes based on the presence (Type I) or absence (Type II) of multiflorin A. Type I contains quercitrin, multinoside A, multiflorin B, and multinoside A acetate as major index compounds. Type II contains hyperin, isoquercitrin, quercetin 3-O-glucuronide, and 3'-methoxy-isoquercitrin as the major index compounds. The chemotype of Rosa section Synstylae (Rosaceae) plants collected in Japan (excluding Tsushima Island) were all classified as Type I with exception of two species, R. luciae and R. sambucina. On the other hand, both Type I and Type II were detected within Rosae fructus obtained from R. multiflora collected in South Korea and Tsushima Island, Japan. The results indicate that Rosae fructus from R. multiflora (Type I) from Japan, excluding Tsushima Island, should be employed clinically, which we describe as purgative.Lead, Jun. 2019, Journal of natural medicines, 73(3) (3), 555 - 565, English, Domestic magazine[Refereed]Scientific journal
- Ophiopogonis Radix (Ophiopogon root), which nourishes the yin, has been used in clinical practice to promote fluid secretion and to moisturize the lungs and skin in traditional Chinese and Japanese (Kampo) medicine. To evaluate this traditional medicinal effect, we investigated the anti-chronic inflammatory effect of Radix Ophiopogonis on senescent cells. Conversely, although several phenotypes of Ophiopogon japonicus Ker-Gawler (Liliaceae) are prevalent in Japan and China, we used these Ophiopogon roots by considering them as one crude drug, Ophiopogonis Radix. In this study, it was revealed that there are two chemotypes (Types A and B) in the root of the original plant, O. japonicus. Methylophiopogonanone A (compound 1) and methylophiopogonanone B (compound 2) were isolated as index compounds from Type A and compound 1 and ophiopogonanone A (compound 3) from Type B. In addition, ophiopogonin B (compound 4) was isolated as the main steroidal saponin from both Type A and B. The results indicated that two different methanol extracts (from Types A and B) and the main constituents of O. japonicus (compound 1-4), significantly downregulated the expression of interleukin (IL)-6 and IL-8, which were enhanced by senescent normal human dermal fibroblasts. Moreover, the two different methanol extracts and compounds 1-4 decreased IL-6 production in a strong and concentration-dependent manner by the ELISA method.Lead, Sep. 2018, Journal of natural medicines, 72(4) (4), 905 - 914, English, Domestic magazine[Refereed]Scientific journal
- (一社)日本TDM学会, Jul. 2025, TDM研究, 42(2) (2), 194 - 194, Japanese新生児が呈した代謝性アルカローシスより母親のトラセミド自己内服が疑われた一例
- (一社)日本臨床腫瘍薬学会, May 2025, 日本臨床腫瘍薬学会雑誌, 41, 164 - 164, Japanese
- 2025, 薬学教育(Web), 9A survey of the educational response to simulated role playing on pharmacy student awareness of pregnancy and medication counselling
- 2025, 日本薬学会年会要旨集(Web), 145thSearch of compounds for the inhibitory effects of melanogenesis caused by fluorouracil
- 2025, 日本薬学会年会要旨集(Web), 145thEstablishment and cellular profile analysis of osimertinib-induced interstitial lung disease model cells
- (一社)日本TDM学会, Jul. 2024, TDM研究, 41(2) (2), 158 - 158, Japanese
- (一社)日本医薬品情報学会, Jun. 2023, 日本医薬品情報学会総会・学術大会講演要旨集, 25回, 147 - 147, Japaneseニルマトレルビル/リトナビル併用時にタクロリムス濃度の異常高値を認めた腎移植症例
- (一社)日本TDM学会, Jun. 2023, TDM研究, 40(2) (2), 176 - 176, Japanese
- 2023, 日本医療薬学会年会講演要旨集(Web), 33rd薬剤師外来が抗血栓薬服用患者の長期臨床アウトカムに与える影響
- 2023, 日本医療薬学会年会講演要旨集(Web), 33rd先天性サイトメガロイウルス感染症患者におけるガンシクロビルのPK/PD解析
- 2023, 日本薬学会年会要旨集(Web), 143rdSearch for compounds increasing the expression of ubiquitin ligase HRD1 and suppressing neuronal cell death
- 2023, 医療薬学フォーラム講演要旨集, 31stパーキンソン病発症に関連する小胞体ストレス関連分子SEL1Lを制御するmicroRNAの探索と血漿中microRNA発現量の検討
- (公社)日本薬学会, Mar. 2020, 日本薬学会年会要旨集, 140年会, 28P - am038, Japaneseがん悪液質に対する補中益気湯による改善効果に関する調査
- (一社)日本生薬学会, Aug. 2019, 日本生薬学会年会講演要旨集, 66回, 184 - 184, JapaneseクロヅルTripterygium regeliiの活性化マクロファージに対する細胞死誘導活性成分の探索
- (公社)日本薬学会, Mar. 2019, 日本薬学会年会要旨集, 139年会(2) (2), 222 - 222, Japanese瀉下作用を持つエイジツの安定供給を目指した国内外における現地調査
- (一社)和漢医薬学会, Sep. 2018, 和漢医薬学会学術大会要旨集, 35回, 129 - 129, Japanese麦門冬のヒト皮膚線維芽細胞を用いたSASPモデルに対する抗炎症作用
- (一社)和漢医薬学会, Aug. 2017, 和漢医薬学会学術大会要旨集, 34回, 109 - 109, Japanese麦門冬のヒト線維芽細胞を用いた細胞老化モデルに対する抗SASP作用
- 日本循環制御医学会, Jun. 2017, 日本循環制御医学会総会プログラム・抄録集, 38回, 115 - 115, Japanese麦門冬のヒト線維芽細胞を用いた細胞老化モデルに対する抗SASP作用
- 日本センブリ研究会, Jun. 2017, 薬用植物研究, 39(1) (1), 16 - 19, Japaneseエイジツ(営実)の持続的安定生産を目的とした品質評価法の検討—45周年記念特別号 ; 薬用植物栽培研究会45周年記念 講演要旨集
- (公社)日本薬学会, Mar. 2017, 日本薬学会年会要旨集, 137年会(2) (2), 192 - 192, Japanese育種を目的としたエイジツ(Rosae Fructus)の化学的品質評価の検討
- 2017, 薬用植物研究, 39(1) (1)秋田県美郷町におけるエイジツ(営実)の持続的安定生産への試み
- 一般社団法人 日本医療薬学会, 23 Oct. 2015, 日本医療薬学会年会講演要旨集, 25, 464, Japanese
- 一般社団法人 日本医療薬学会, 23 Oct. 2015, 日本医療薬学会年会講演要旨集, 25, 464, Japanese
- 一般社団法人 日本医療薬学会, 23 Oct. 2015, 日本医療薬学会年会講演要旨集, 25, 464, Japanese
- (公社)日本薬学会, Mar. 2015, 日本薬学会年会要旨集, 135年会(4) (4), 65 - 65, Japanese胃運動促進薬、食前酒、喫煙が健常者胃運動機能に及ぼす影響
■ Lectures, oral presentations, etc.
- 第45回日本病院薬剤師会近畿学術大会, Japaneseブレクスピプラゾール、クエチアピンおよびリスペリドンを服用中の妊婦とその児における薬物動態の評価Poster presentation
- 第33回日本医療薬学会年会, Japanese先天性サイトメガロイウルス感染症患者におけるガンシクロビルのPK/PD解析Oral presentation
- 第33回日本医療薬学会年会, Japanese薬剤師外来が抗血栓薬服用患者の長期臨床アウトカムに与える影響Oral presentation
- 第33回日本医療薬学会年会, EnglishEffect of early dose reduction of osimertinib on efficacy in the first-line treatment for EGFR-positive non-small cell lung cancerOral presentation
- 21st International Congress of Therapeutic Drug Monitoring and Clinical Toxicology, EnglishA model-based pharmacokinetic analysis of drug-drug interaction between nirmatrelvir/ritonavir and tacrolimusPoster presentation
- 医療薬学フォーラム2023/第31回クリニカルファーマシーシンポジウム, Japaneseパーキンソン病発症に関連する小胞体ストレス関連分子SEL1Lを制御するmicroRNAの探索と血漿中microRNA発現量の検討
- TDM研究, Jun. 2023, Japanese, (一社)日本TDM学会高度腎機能低下患者におけるバンコマイシンAUC-guided TDMの安全性に関する検討
- 日本医薬品情報学会総会・学術大会講演要旨集, Jun. 2023, Japanese, (一社)日本医薬品情報学会ニルマトレルビル/リトナビル併用時にタクロリムス濃度の異常高値を認めた腎移植症例
- 日本薬学会第143年会, JapaneseユビキチンリガーゼHRD1を誘導する化合物の探索と神経細胞死抑制効果の検討Oral presentation
- 日本薬学会年会要旨集, Mar. 2020, Japanese, (公社)日本薬学会がん悪液質に対する補中益気湯による改善効果に関する調査
- 日本生薬学会年会講演要旨集, Aug. 2019, Japanese, (一社)日本生薬学会クロヅルTripterygium regeliiの活性化マクロファージに対する細胞死誘導活性成分の探索
- 日本薬学会年会要旨集, Mar. 2019, Japanese, (公社)日本薬学会瀉下作用を持つエイジツの安定供給を目指した国内外における現地調査
- 和漢医薬学会学術大会要旨集, Sep. 2018, Japanese, (一社)和漢医薬学会麦門冬のヒト皮膚線維芽細胞を用いたSASPモデルに対する抗炎症作用
- 和漢医薬学会学術大会要旨集, Aug. 2017, Japanese, (一社)和漢医薬学会麦門冬のヒト線維芽細胞を用いた細胞老化モデルに対する抗SASP作用
- 薬用植物研究, Jun. 2017, Japanese, 日本センブリ研究会エイジツ(営実)の持続的安定生産を目的とした品質評価法の検討—45周年記念特別号 ; 薬用植物栽培研究会45周年記念 講演要旨集
- 日本循環制御医学会総会プログラム・抄録集, Jun. 2017, Japanese, 日本循環制御医学会麦門冬のヒト線維芽細胞を用いた細胞老化モデルに対する抗SASP作用
- 日本薬学会年会要旨集, Mar. 2017, Japanese, (公社)日本薬学会育種を目的としたエイジツ(Rosae Fructus)の化学的品質評価の検討
- 薬用植物研究, 2017秋田県美郷町におけるエイジツ(営実)の持続的安定生産への試み
- 日本医療薬学会年会講演要旨集, Oct. 2015, Japanese, 一般社団法人 日本医療薬学会P1191-22-PM アルコール依存症患者の過去26年間における年齢分布および上部消化管疾患の変移(精神科領域,ポスター発表,一般演題,医療薬学の進歩と未来-次の四半世紀に向けて-)
- 日本医療薬学会年会講演要旨集, Oct. 2015, Japanese, 一般社団法人 日本医療薬学会P1189-22-PM アルコール依存症患者における腹部超音波所見・血液検査所見と飲酒期間との相関(精神科領域,ポスター発表,一般演題,医療薬学の進歩と未来-次の四半世紀に向けて-)
- 日本医療薬学会年会講演要旨集, Oct. 2015, Japanese, 一般社団法人 日本医療薬学会P1190-23-AM アルコール依存症患者における長期アルコール摂取と合併症との相関(精神科領域,ポスター発表,一般演題,医療薬学の進歩と未来-次の四半世紀に向けて-)
- 日本薬学会年会要旨集, Mar. 2015, Japanese, (公社)日本薬学会胃運動促進薬、食前酒、喫煙が健常者胃運動機能に及ぼす影響
