Yakugaku zasshi : Journal of the Pharmaceutical Society of Japan最新文献

{"title":"[Development of a Novel Therapeutic for Pediatric Heart Failure Targeting Angiotensin II Receptor].","authors":"Hiroyuki Kawagishi, Takero Nakajima, Risa Ramadhiani, Tsutomu Nakada, Takuro Tomita, Yasunari Kanda, Noriaki Emoto, Mitsuhiko Yamada","doi":"10.1248/yakushi.24-00171-1","DOIUrl":"10.1248/yakushi.24-00171-1","url":null,"abstract":"<p><p>Pediatric drug development is a global challenge. Children undergo organ growth and exhibit different drug reactions than adults, resulting in different pharmacological responses. Therefore, it is necessary to consider children's physiological characteristics when evaluating drug efficacy and safety in pediatric patients. We conducted drug discovery research for the treatment of pediatric heart failure, based on neonatal-specific physiological functions of angiotensin II. Pediatric heart failure is one of the most important causes of death in children, particularly neonates and infants. However, only a few therapeutic agents are available to treat pediatric heart failure. Angiotensin II binds to its receptors (angiotensin II receptor type 1: AT₁R) and regulates cellular functions through G protein and β-arrestin pathways. We previously found that the β-arrestin-biased AT₁R agonist, TRV027, induced a positive inotropic effect in the hearts of neonatal mice. Acute administration of TRV027 did not affect heart rate, oxygen consumption, or production of reactive oxygen species. The inotropic effect of TRV027 was also observed in human iPS cell-derived cardiomyocytes and a neonatal mouse model of dilated cardiomyopathy. Furthermore, chronic administration of TRV027 improved the survival rate of mice with dilated cardiomyopathy during the preweaning period. These results demonstrate that TRV027 has the potential to be a safe and effective drug for treating pediatric heart failure.</p>","PeriodicalId":23810,"journal":{"name":"Yakugaku zasshi : Journal of the Pharmaceutical Society of Japan","volume":"145 4","pages":"275-280"},"PeriodicalIF":0.3,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143773242","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"[Neonatal Malnutrition Impacts Fibroblast Growth Factor 21-induced Neurite Outgrowth and Growth Hormone-releasing Hormone Secretion in Neonatal Mouse Brain].","authors":"Yuko Yoshida, Ai Shinomiya, Mana Oikawa, Taiga Shimada, Ken-Ichi Hanaki, Yoshifumi Watanabe","doi":"10.1248/yakushi.24-00177-3","DOIUrl":"10.1248/yakushi.24-00177-3","url":null,"abstract":"<p><p>Neonatal malnutrition has been suggested as a factor contributing to neurological and other disorders. However, the details of this mechanism remain unclear. We focused on fibroblast growth factor 21 (FGF21), an endocrine factor produced in the liver during lactation-the main source of nutrition during the neonatal period- and analyzed its role in the brain. From the RNA-seq analysis of mouse brains, we analyzed the genes whose expression was regulated by FGF21 and their respective functions. We found that FGF21 has two functions in the neonatal brain; FGF21 induces the production of growth hormone-releasing hormone (GHRH) in the hypothalamus and is involved in isoform determination of Kalirin, a Ras homologous guanine nucleotide exchange factor, and promotes neurite outgrowth in the brain. Furthermore, the above mechanism is regulated by SH2-containing tyrosine phosphatase (SHP2) activity downstream of the FGF receptor. Additionally, the conserved intron of the SHP2 gene, Ptpn11, shows altered activity in malnourished mouse brains. In summary, FGF21 functions in neurite outgrowth and GHRH production in the neonatal mouse brain, with the mechanism being regulated by SHP2. However, SHP2 activity depends on nutritional status. Our goal was to elucidate the mechanisms by which FGF21 is involved in the maintenance of the central nervous system during the neonatal period. This study provides new insights into the role of FGF21 in diseases caused by dysfunction due to malnutrition.</p>","PeriodicalId":23810,"journal":{"name":"Yakugaku zasshi : Journal of the Pharmaceutical Society of Japan","volume":"145 3","pages":"183-188"},"PeriodicalIF":0.3,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143538018","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"[Beyond Borders: Next-generation Technologies for Analytical Chemistry and Drug Development].","authors":"Hiroki Akiba, Eisuke Kanao","doi":"10.1248/yakushi.24-00186-F","DOIUrl":"https://doi.org/10.1248/yakushi.24-00186-F","url":null,"abstract":"","PeriodicalId":23810,"journal":{"name":"Yakugaku zasshi : Journal of the Pharmaceutical Society of Japan","volume":"145 6","pages":"515-516"},"PeriodicalIF":0.3,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144200205","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"[The Impact of a Picture Book to Improve Medication Compliance in Pediatric Patients: A Questionnaire Survey].","authors":"Kensuke Yoshida, Anna Kiyomi, Suguru Tohyama, Kanami Take, Takuma Shoji, Yonggon Lee, Kyongsun Pak, Munetoshi Sugiura","doi":"10.1248/yakushi.24-00132","DOIUrl":"10.1248/yakushi.24-00132","url":null,"abstract":"<p><p>Poor medication compliance in children can affect treatment efficacy. We examined the impact of a picture book created by pharmacists to improve medication compliance in children. Our study aim was to assess the effects of the pharmacist-created picture book on medication compliance in children and their parents in collaboration with an outpatient pharmacy. This study included 74 children [recovery rate 28/74 (37.8%)] aged 3-6 years and their parents between March 2023 and March 2024. In the item \"Have you experienced any difficulties in giving medication to your child?\" the proportion of respondents answering, \"Always\" or \"Sometimes\" decreased from 78.3% (18/23) to 34.7% (8/23) after reading the picture book (p<0.01). When answering the question \"What specific situations have you found challenging when giving medication?\" the number of responses decreased from (an average/mean) of 1.5 situations before reading the picture book to 1 situation. Regarding whether guardians felt a greater appreciation for the importance of giving medication to their children after reading the book, 64.3% answered \"Yes,\" the highest response. A positive correlation (correlation coefficient=0.77, p<0.01) was observed between \"Is the child interested in taking the medication?\" and \"Is the child able to take the medicine? Pharmacists need to raise public awareness of the importance of medication adherence. Since picture books are likely to be repeatedly read aloud, they are considered effective. The results of this study suggest that pharmacist-created picture books may contribute to improving medication compliance in children.</p>","PeriodicalId":23810,"journal":{"name":"Yakugaku zasshi : Journal of the Pharmaceutical Society of Japan","volume":" ","pages":"1031-1037"},"PeriodicalIF":0.3,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142112717","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"[Development of an Odor Evaluation Method for Citrus Unshiu Peel Using an Electronic Nose Based on the Intensity of Per Unit Length (INPULTH)].","authors":"Yoshitomi Kudo, Fukuyo Tanaka, Kouki Fujioka","doi":"10.1248/yakushi.24-00074","DOIUrl":"10.1248/yakushi.24-00074","url":null,"abstract":"<p><p>Although odor is an important indicator of herbal medicine quality, an objective odor evaluation method remains undiscovered. Quantitative measurement using previous methods is complicated as Citrus Unshiu Peel (Chimpi) emits an odor when broken. To establish odor evaluation methods for herbal medicines using chimpi as an example, we developed a reproducible method for breaking samples and an objective odor evaluation method using an electronic nose (e-nose). First, an odor-emitting device (OED) was fabricated by modifying a pill cutter, which suppressed the spread of odor components into the room air while cutting the samples. The odor was emitted from chimpi with an OED and measured using an e-nose. The cut length was then measured. The sensor intensity was positively correlated with the cut length (r=0.840-0.927) in the same sample, and the intensity per unit length (INPULTH) calculated from the sensor intensity and cut length enables the comparison of the sensor intensity among different samples. In addition, average d-limonene emission level measured by GC-MS was positively correlated with average INPULTH (r=0.999), which suggests that this OED and e-nose method enables the comparison of the sensor intensity and d-limonene emissions. INPULTH also positively correlated with other seven monoterpenes such as p-cymene, β-myrcene, β-phellandrene, α-pinene, β-pinene, γ-terpinene, and α-terpinolene (r=0.701-0.865). Therefore, monoterpene content can be evaluated by measuring the odor in the same way as d-limonene. In conclusion, we developed a simple odor intensity evaluation method optimized for chimpi to establish an odor evaluation method for herbal medicines.</p>","PeriodicalId":23810,"journal":{"name":"Yakugaku zasshi : Journal of the Pharmaceutical Society of Japan","volume":" ","pages":"1019-1029"},"PeriodicalIF":0.3,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142156116","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"[What is the Initiating Reaction for the Lipid Radical Chain Reaction System That Can Induce Ferroptotic Cell Death at the Lower Oxygen Content?]","authors":"Ichiro Koshiishi","doi":"10.1248/yakushi.23-00207","DOIUrl":"10.1248/yakushi.23-00207","url":null,"abstract":"<p><p>The neural cell death in cerebral infarction is suggested to be ferroptosis-like cell death, involving the participation of 15-lipoxygenase (15-LOx). Ferroptosis is induced by lipid radical species generated through the one-electron reduction of lipid hydroperoxides, and it has been shown to propagate intracellularly and intercellularly. At lower oxygen concentration, it appeared that both regiospecificity and stereospecificity of conjugated diene moiety in lipoxygenase-catalysed lipid hydroperoxidation are drastically lost. As a result, in the reaction with linoleic acid, the linoleate 9-peroxyl radical-ferrous lipoxygenase complex dissolves into the linoleate 9-peroxyl radical and ferrous 15-lipoxygenase. Subsequently, the ferrous 15-lipoxygenase then undergoes one-electron reduction of 13-hydroperoxy octadecadienoic acid, generating an alkoxyl radical (pseudoperoxidase reaction). A part of the produced lipid alkoxyl radicals undergoes cleavage of C-C bonds, liberating small molecular hydrocarbon radicals. Particularly, in ω-3 polyunsaturated fatty acids, which are abundant in the vascular and nervous systems, the liberation of small molecular hydrocarbon radicals was more pronounced compared to ω-6 polyunsaturated fatty acids. The involvement of these small molecular hydrocarbon radicals in the propagation of membrane lipid damage is suggested.</p>","PeriodicalId":23810,"journal":{"name":"Yakugaku zasshi : Journal of the Pharmaceutical Society of Japan","volume":" ","pages":"431-439"},"PeriodicalIF":0.3,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139513791","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"[Exploration of Risk Factors of the Onset of Antibiotics-induced Acute Kidney Injury and Its Transfer to Chronic Kidney Disease Using the Medical Information Database].","authors":"Masaya Ieda, Yuka Kuroda, Takahiro Matsumoto, Ayaka Yamashita, Takashi Watanabe, Katsuhito Hori, Michio Kimura, Junichi Kawakami, Masahiro Tohkin","doi":"10.1248/yakushi.23-00198","DOIUrl":"10.1248/yakushi.23-00198","url":null,"abstract":"<p><p>Drug-induced acute kidney injury (AKI) is a serious adverse drug reaction, which results in a significant decline in renal function and is known to progress to chronic kidney disease (CKD). Therefore, appropriate drug therapy is important to avoid the risk of drug-induced AKI and CKD, which are serious concerns in clinical practice. In this study, using the medical information database of Hamamatsu University Hospital, we investigated the risk factors that accelerate the onset of drug-induced AKI or its progression to CKD in patients who received aminoglycoside antibiotics (AGs) or glycopeptide antibiotics (GPs), which are strongly associated with drug-induced AKI and CKD. We performed logistic regression analysis using patients' background, laboratory test results, and concomitant drug use, among other such factors as explanatory variables and drug-induced AKI or CKD onset as objective variables to explore the risk factors for drug-induced AKI and CKD. Our results showed that co-administration of amphotericin B, piperacillin-tazobactam and other AGs and GPs, increased serum creatinine (Scr) and chloride concentrations, serum lactate dehydrogenase activity, and decreased serum albumin concentration were risk factors for drug-induced AKI onset. Moreover, a reduced blood urea nitrogen : Scr ratio at drug-induced AKI onset served as a risk factor for CKD. These results suggest that careful monitoring of the aforementioned factors is important to ensure appropriate usage of these drugs in patients treated with AGs and GPs.</p>","PeriodicalId":23810,"journal":{"name":"Yakugaku zasshi : Journal of the Pharmaceutical Society of Japan","volume":" ","pages":"447-462"},"PeriodicalIF":0.3,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139546786","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"[Xanthan Gum-based Food Thickeners Reduce Disintegration Time of Medical and OTC Loxoprofen Sodium Tablets].","authors":"Masami Kawahara, Maika Moriyama, Misato Fukatsu, Motozumi Ando, Norio Watanabe","doi":"10.1248/yakushi.23-00148","DOIUrl":"10.1248/yakushi.23-00148","url":null,"abstract":"<p><p>Xanthan gum-based food thickeners have been reported to potentially interfere with tablet disintegration. Loxoprofen sodium (LOX) is widely used as an antipyretic analgesic and is expected to provide rapid pain relief. In this study, we aimed to investigate the impact of a xanthan gum-based food thickener on LOX tablet disintegration. We used four different brands each of medical and OTC-LOX tablets, each containing 60 mg of LOX as the sole active ingredient. Depending on the brand, tablet hardness varied between 50.1-96.6 N and was not associated with the disintegration time. Disintegration times for medical tablets not immersed in the food thickener were 536±215, 621±159, 348±22, 369±42 s and for OTC tablets, were 358±20, 336±13, 292±13, 172±27 s. Immersion in the food thickener for 15 min reduced medical tablet disintegration time to 177±46 and 233±150 s (the third and fourth brands were disintegrated during immersion), and that for OTC tablets to 77±40, 75±110, and 37±85 s (the fourth brand was disintegrated during immersion). Despite each tablet containing different pharmaceutical additives, no correlation was found between disintegration time and presence of superdisintegrants. The OTC tablet with a light anhydrous silicic acid coating exhibited the shortest disintegration time. Thus, the disintegration time of LOX tablets is accelerated when immersed in the xanthan gum-based food thickener, potentially leading to rapid pain relief for patients.</p>","PeriodicalId":23810,"journal":{"name":"Yakugaku zasshi : Journal of the Pharmaceutical Society of Japan","volume":" ","pages":"231-237"},"PeriodicalIF":0.3,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138441271","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cost of Pegfilgrastim for the Prophylaxis of Chemotherapy-induced Febrile Neutropenia in Patients with Breast Cancer Receiving Perioperative Chemotherapy in Daily Practice in Japan: A Posthoc Analysis in a Single-center Retrospective Study.","authors":"Takuya Tomomatsu, Hisanori Shimizu, Takashi Yokokawa, Ippei Fukada, Kazuyoshi Kawakami, Kazuo Kobayashi, Takeshi Aoyama, Wataru Suzuki, Takahito Sugisaki, Koki Hashimoto, Maimi Asano, Yuka Mori, Fumikata Hara, Toshimi Takano, Shinji Ohno, Masakazu Yamaguchi","doi":"10.1248/yakushi.24-00030","DOIUrl":"https://doi.org/10.1248/yakushi.24-00030","url":null,"abstract":"<p><p>This study aimed to estimate the medical costs associated with febrile neutropenia (FN) prophylaxis with pegfilgrastim and evaluate its impact on survival outcomes in daily practice in Japan. In this single-center retrospective study, we obtained data from 296 Japanese patients with breast cancer receiving fluorouracil, epirubicin, and cyclophosphamide (FEC)-100 chemotherapy; the patients were divided into the pegfilgrastim and non-pegfilgrastim groups. We analyzed the median costs of chemotherapy, drugs for all adverse events (AEs) and FN, and hospitalization due to FN. We also assessed the survival outcomes. The pegfilgrastim group showed a significantly higher median total cost (JPY 872320.0 vs. JPY 466715.0, p<0.001). This difference was associated with the prophylactic use of pegfilgrastim. The median costs of the drugs for all AE treatments were JPY 9030.4 and JPY 24690.6, with the non-pegfilgrastim group showing a significantly higher cost (p<0.001). In 11 patients hospitalized for FN management, no significant difference in hospitalization cost was observed between the pegfilgrastim and non-pegfilgrastim groups (JPY 512390.0 vs. JPY 307555.0, p=0.102). No significant difference in the 3-year overall survival was observed between the pegfilgrastim and non-pegfilgrastim groups (79.9% vs. 88.3%, p=0.672). In this study, although the total medical cost in daily practice increased because of primary prophylaxis with pegfilgrastim, the 3-year overall survival was not impacted by the use of pegfilgrastim. Our study data suggested that the primary prophylaxis pegfilgrastim should be used during FEC-100 chemotherapy based on the patient-related FN risk factors, instead of routine use.</p>","PeriodicalId":23810,"journal":{"name":"Yakugaku zasshi : Journal of the Pharmaceutical Society of Japan","volume":"144 9","pages":"897-904"},"PeriodicalIF":0.3,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142112725","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"[Quality of Life Based Health Economics Research on Pharmaceutical Intervention in Cancer Chemotherapy].","authors":"Kazuhide Tanaka","doi":"10.1248/yakushi.24-00090","DOIUrl":"https://doi.org/10.1248/yakushi.24-00090","url":null,"abstract":"<p><p>The adverse chapter of cancer chemotherapy negatively impact QOL, and pharmacists play a key role in improving QOL by providing optimal drug therapy through pharmaceutical interventions. Although outpatient cancer chemotherapy is now common, the impact of pharmaceutical interventions from a QOL perspective has not been thoroughly studied. Therefore, this study investigated the impact and cost-effectiveness of pharmaceutical interventions on QOL using the EuroQol 5 Dimension (EQ-5D) and Quality of Life Questionnaire for Cancer Patients Treated with Anticancer Drugs (QOL-ACD). The study was conducted between 2013 and 2015 on 39 patients who underwent their first outpatient chemotherapy for breast cancer at Gifu Municipal Hospital. The results showed that pharmaceutical interventions improved social relationship QOL in patients experiencing fatigue during the first cycle and enhanced psychological QOL in patients with adverse events of nausea during the second cycle. Furthermore, the maximum incremental cost-effectiveness ratio (ICER) was found to be 1.3 million yen per quality-adjusted life years (QALY) according to cost utility analysis. The pharmaceutical interventions by pharmacists in outpatient cancer chemotherapy improve QOL, and the ICER remains well below the Japanese threshold, signifying clear medical and economic benefits.</p>","PeriodicalId":23810,"journal":{"name":"Yakugaku zasshi : Journal of the Pharmaceutical Society of Japan","volume":"144 11","pages":"973-976"},"PeriodicalIF":0.3,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142576875","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}