{"title":"[Preparation of Degraded Microplastics That Imitate Surface Properties in the Environment].","authors":"Hirofumi Tsujino, Yudai Ikuno, Yuya Haga, Haruyasu Asahara, Kazuma Higashisaka, Yasuo Tsutsumi","doi":"10.1248/yakushi.23-00152-2","DOIUrl":"10.1248/yakushi.23-00152-2","url":null,"abstract":"<p><p>Microplastics are small pieces of plastic that are less than 5 mm in length. These plastics have been detected in various environments, including the ocean, soil, and air. Their abundance have raised concerns regarding their potential effects on living organisms, including humans. The surface of microplastics degrades due to external factors such as ultraviolet rays and water waves in the environment. Therefore, assessing the biological impact of microplastics and considering their state of degradation is important. Among the physical properties of microplastics, we focused on the chemical degradation of microplastics. Specifically, we used vacuum ultraviolet (VUV) light to accelerate the degradation of polyethylene (PE) and prepared PE samples representing the degradation of PE to varying degrees. The surface properties of PE samples prepared using VUV were similar to those obtained from the environment. Cytotoxicity tests were then used to evaluate the effects of undegraded and degraded PE on cells. We found that the severity of cytotoxicity increased with the extent to which the PE would have been degraded, suggesting that the degree of degradation is strongly linked to the severity of the observed deleterious effects on living organisms. In conclusion, this finding contributes to our understanding of the effects of polyethylene microplastics on the human body.</p>","PeriodicalId":23810,"journal":{"name":"Yakugaku zasshi : Journal of the Pharmaceutical Society of Japan","volume":"144 2","pages":"171-175"},"PeriodicalIF":0.3,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139698433","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":"[Toward Elucidation of Human Health Effects of Micro/nanoplastics].","authors":"Yasuo Tsutsumi, Hirofumi Tsujino","doi":"10.1248/yakushi.23-00152-F","DOIUrl":"10.1248/yakushi.23-00152-F","url":null,"abstract":"","PeriodicalId":23810,"journal":{"name":"Yakugaku zasshi : Journal of the Pharmaceutical Society of Japan","volume":"144 2","pages":"163-164"},"PeriodicalIF":0.3,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139698434","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":"Evaluation of Sources of Drug Interaction Information for Nirmatrelvir/ritonavir.","authors":"Hiroshi Yoshikawa, Takashi Tomita, Erika Shigita, Hanae Takamatsu, Aoi Matsushima, Tokue Yanagida, Hiroaki Matsuo","doi":"10.1248/yakushi.23-00204","DOIUrl":"https://doi.org/10.1248/yakushi.23-00204","url":null,"abstract":"<p><p>The Japanese package insert (J-PI) for nirmatrelvir/ritonavir (N/r) (specially approved pharmaceutical) includes numerous warnings about drug interactions. However, discrepancies in the information on drug interaction are reported between J-PI and foreign databases. This study aimed to evaluate various information sources on N/r drug interactions. We categorized and compared information on N/r drug interactions from the J-PI, prescribing information from foreign regulatory agencies, guidance from the National Institutes of Health and University Health Network, the Ontario coronavirus disease 2019 (COVID-19) Science Advisory Table, University of Liverpool, Lexicomp, and the Japanese Society of Pharmaceutical Health Care and Sciences (JSPHCS). We assessed information quantity, missing data in J-PI, predicted change of the area under the blood concentration-time curve (AUC) for nirmatrelvir or co-administered drugs, and the information source consistency. From these information sources, we compiled a dataset with 115 contraindications and 203 precautions for N/r co-administration, and 51 contraindications are missing in J-PI. Among them, at least 12 drugs have large predicted AUC changes with N/r (AUC ≥5-fold or <1/5 of the baseline value). Nine of these 12 drugs are included as contraindications in Lexicomp and the JSPHCS. The consistency among the information sources is low. Information in the J-PI alone may be insufficient and Lexicomp or the JSPHCS guidelines should be useful because of their large amounts of information and wide coverage of drugs with large AUC changes. Due to low source consistency, multiple sources are needed for clinical management.</p>","PeriodicalId":23810,"journal":{"name":"Yakugaku zasshi : Journal of the Pharmaceutical Society of Japan","volume":"144 7","pages":"733-740"},"PeriodicalIF":0.3,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141471158","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":"[Considering the Professionalism of Pharmacists].","authors":"Masahiro Okuda, Tetsumi Irie","doi":"10.1248/yakushi.23-00172-F","DOIUrl":"https://doi.org/10.1248/yakushi.23-00172-F","url":null,"abstract":"","PeriodicalId":23810,"journal":{"name":"Yakugaku zasshi : Journal of the Pharmaceutical Society of Japan","volume":"144 6","pages":"585-586"},"PeriodicalIF":0.3,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141200699","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":"Speed and Accuracy of Recording Medication History by Pharmacists in Secondary Emergency Rooms.","authors":"Hiroki Tateishi, Youhei Yano, Takao Goto, Daisuke Miyazu, Hiroyuki Watanabe","doi":"10.1248/yakushi.23-00215","DOIUrl":"https://doi.org/10.1248/yakushi.23-00215","url":null,"abstract":"<p><p>In Japan, only few hospitals have pharmacists in their secondary emergency rooms to record medication history and provide drug information in real time. In this study, we investigated the benefits of pharmacist intervention in secondary emergency rooms by comparing the time taken by the pharmacists and non-pharmacists in the emergency room to record the medication history in the electronic medical record and the accuracy of its content. The study period was from September 1 to September 30, 2022, and included patients who were transported to our hospital for emergency care between 9:00 and 16:30. We compared the time taken between the patient's arrival until the recording of their medication history and the accuracy of the record by the emergency room pharmacists and non-pharmacists (paramedics or medical clerks). The study included 58 patients whose medication histories were collected by pharmacists, and 11 patients whose histories were collected by non-pharmacists. For pharmacists, the median time to record medication history in the electronic medical record was 12 min, whereas for non-pharmacists, it was 19 min, which was significantly different (p=0.015). The pharmacists accurately recorded the medication history of 98.3% (57/58) of patients, whereas non-pharmacists accurately recorded it for only 54.5% (6/11) of patients, with a significant difference (p<0.01). We observed that in secondary emergency rooms, when pharmacists were responsible for recording the patients' medication histories, it resulted in rapid and accurate sharing of medication history.</p>","PeriodicalId":23810,"journal":{"name":"Yakugaku zasshi : Journal of the Pharmaceutical Society of Japan","volume":"144 6","pages":"691-695"},"PeriodicalIF":0.3,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141200654","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":"[Advances in the Pathophysiology and Drug Discovery of Novel Therapeutics for Attention-Deficit/hyperactivity Disorder].","authors":"Hiroki Shikanai","doi":"10.1248/yakushi.24-00126","DOIUrl":"10.1248/yakushi.24-00126","url":null,"abstract":"<p><p>Attention-deficit/hyperactivity disorder (ADHD) is a neurodevelopmental disorder characterized by inattention, hyperactivity and impulsivity. Psychostimulants such as methylphenidate are first-line treatments, but carry risks of severe side effects and addiction. Therefore, further research and the discovery of non-psychostimulant medications with novel mechanisms are urgently needed. We previously reported that juvenile stroke-prone spontaneously hypertensive rats (SHRSP/Ezo) are a suitable animal model of ADHD, and we identified N-methyl-D-aspartate (NMDA) receptor dysfunction in the prefrontal cortex of SHRSP/Ezo. D-Serine, a co-agonist for the glycine binding site of NMDA receptors, is synthesized from L-serine by serine racemase (SR) and degraded by D-amino acid oxidase (DAAO). Although D-serine dysregulation is implicated in psychiatric disorders, its pathophysiological role in ADHD is unclear. We measured D-serine in the medial prefrontal cortex (mPFC) of SHRSP/Ezo and addressed SR and DAAO expression. Additionally, we assessed cognitive function following DAAO inhibitor microinjection into the mPFC. SHRSP/Ezo showed a reduced D-serine/total serine (DL) ratio in the mPFC compared with the genetic control, Wistar Kyoto rat/Ezo (WKY/Ezo). DAAO expression in the mPFC was higher in SHRSP/Ezo rats compared with WKY/Ezo, however there was no difference in SR expression. The microinjection of a DAAO inhibitor into the mPFC of SHRSP/Ezo rats increased the DL ratio and ameliorated ADHD-like behaviors in the Y-maze test. These results suggest an association between abnormal D-serine metabolism and ADHD-like behaviors based on NMDA receptor dysfunction in the mPFC. Our findings provide insight into ADHD pathogenesis and should advance the development of new therapeutic approaches for the disorder.</p>","PeriodicalId":23810,"journal":{"name":"Yakugaku zasshi : Journal of the Pharmaceutical Society of Japan","volume":"144 12","pages":"1039-1044"},"PeriodicalIF":0.3,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142772856","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":"Effect of Perioperative Docetaxel-induced Limb Edema on Health-related Quality of Life in Patients with Early-stage Breast Cancer: A Prospective Observational Study.","authors":"Kaori Matsumoto, Yoshihito Morimoto, Junichiro Wakatsuki, Daiki Sakuma, Keiko Mukouyama, Masayuki Inoue, Ayako Kimura, Iori Hirosawa, Kazuhiro Watanabe","doi":"10.1248/yakushi.23-00206","DOIUrl":"10.1248/yakushi.23-00206","url":null,"abstract":"<p><p>Docetaxel (DTX) is a key drug used in perioperative chemotherapy for breast cancer. Edema is a known adverse effect of DTX, but its effect on health-related QOL (HRQOL) is unclear. In this study, we evaluated the effects of edema caused by administration of DTX on HRQOL in patients with early-stage breast cancer. We prospectively investigated patients diagnosed with early-stage breast cancer (stage I-III) who received 4 cycles of DTX as preoperative or postoperative chemotherapy between September 2021 and December 2022 at Yamanashi Prefectural Central Hospital. The circumference of each extremity was measured at each administration of DTX, and limb edema was evaluated by Common Terminology Criteria for Adverse Events version 5.0. HRQOL was evaluated using SF-12 version 2, which has a range of 0-100 (national standard, 50), and compared between the presence and absence of grade 2 or higher edema and between before and after administration of DTX. Twenty patients met the eligibility criteria and were included in the study. There was no difference in the HRQOL score according to whether grade 2 limb edema was present. The median HRQOL summary scores before and after administration of DTX were 51.1 and 50.8 (p=0.763), respectively, for mental health, 52.6 and 49.4 (p=0.005) for physical health, and 38.9 and 37.5 (p=1.000) for role/social health. We found no direct effect of DTX-induced limb edema on HRQOL in patients with early-stage breast cancer. However, HRQOL summary scores indicated that administration of DTX reduced physical health in these patients.</p>","PeriodicalId":23810,"journal":{"name":"Yakugaku zasshi : Journal of the Pharmaceutical Society of Japan","volume":"144 6","pages":"685-690"},"PeriodicalIF":0.3,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141200652","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}
Kyohei Yoshida, Go Morikawa, Ken Kubota, Katsuko Okazawa
{"title":"[Assessing the Impact of in-Hospital Formulary Policies on the Prescription Patterns of Direct Oral Anticoagulants (DOACs)].","authors":"Kyohei Yoshida, Go Morikawa, Ken Kubota, Katsuko Okazawa","doi":"10.1248/yakushi.24-00078","DOIUrl":"https://doi.org/10.1248/yakushi.24-00078","url":null,"abstract":"<p><p>Prescribing direct oral anticoagulants (DOACs) with off-label dosage and administration is discouraged due to concerns about their effectiveness and safety. Consequently, our hospital pharmacist established a formulary with physicians for oral anticoagulants. Our study aimed to assess the adherence to this formulary by investigating the rate of appropriate DOAC prescribing. We included patients who were newly prescribed or continued on DOACs (dabigatran, rivaroxaban, apixaban, and edoxaban) at our hospital. We calculated the percentage of patients prescribed the correct dosage and administration according to the package insert and compared this across three time periods: pre-intervention (period A; April-September 2019), post-intervention phase 1 (period B; August 2021-January 2022), and post-intervention phase 2 (period C; November 2022-April 2023). We also examined the number of inquiries and consultation requests made by hospital pharmacists regarding DOAC dosage and administration. A total of 782 patients were surveyed (191 in period A, 263 in period B, and 328 in period C). The appropriate prescribing rates for DOACs were 79.1% in period A, 84.4% in period B, and 86.6% in period C. The proportion of cases where hospital pharmacists questioned or consulted doctors about DOAC dosage and administration was 3.7% in period A, 6.1% in period B, and 10.1% in period C. These findings indicate that active intervention by hospital pharmacists using the formulary regarding oral anticoagulant formularies may promote appropriate DOAC use.</p>","PeriodicalId":23810,"journal":{"name":"Yakugaku zasshi : Journal of the Pharmaceutical Society of Japan","volume":"144 10","pages":"945-950"},"PeriodicalIF":0.3,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142366738","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":"[Identification of Δ<sup>8</sup>-Tetrahydrocannabinol (THC) and Δ<sup>9</sup>-THC Analogs, with Different Lengths of Alkyl Chain at C-3 Position, in Oil Products Distributed on the Internet].","authors":"Rie Tanaka, Ruri Kikura-Hanajiri","doi":"10.1248/yakushi.24-00029","DOIUrl":"https://doi.org/10.1248/yakushi.24-00029","url":null,"abstract":"<p><p>Since around 2021, products claiming to contain a Δ<sup>9</sup>-tetrahydrocannabinol (THC) analog with different lengths of alkyl chain at C-3 position have been sold on the internet in Japan. Δ<sup>9</sup>-THC has a pentyl group derived from the precursor olivetol at the C-3 position. These products include liquid cartridges for electronic cigarettes, herbal products, and gummy products. This study analyzed and determined the ingredients in five oil products distributed on the internet from 2022 to 2023 that claim to contain THC analogs. Samples of each product were used for GC-MS and LC-MS measurements. After isolating and purifying the unknown components from the products, structural analysis was performed by measuring <sup>1</sup>H, <sup>13</sup>C-NMR and various two-dimensional NMR [HH correlation spectroscopy (H-H COSY), heteronuclear multiple quantum coherence (HMQC), heteronuclear multiple-bond correlation (HMBC), and nuclear Overhauser effect spectroscopy (NOESY)]. The analysis identified Δ<sup>8</sup>-tetrahydrocannabivarin (THCV), Δ<sup>9</sup>-THCV, Δ<sup>8</sup>-tetrahydrocannabutol (THCB), Δ<sup>9</sup>-THCB, Δ<sup>8</sup>-tetrahydrocannabihexol (THCH), Δ<sup>9</sup>-THCH, Δ<sup>8</sup>-3-octyl-THC (THCjd) and Δ<sup>9</sup>-THCjd. These compounds were Δ<sup>8</sup>-THC or Δ<sup>9</sup>-THC analogs with different lengths of alkyl chain at C-3 position. Meanwhile, Δ<sup>4(8)</sup>-iso-THCV and Δ<sup>11</sup>-THCB were identified as minor components of the product, and were considered to be the reaction byproducts of the synthesis of the Δ<sup>8</sup>-THC or Δ<sup>9</sup>-THC analogs. In the future, there are concerns about the distribution of products containing new THC analogs. Therefore, continuous provision monitoring of newly detected in the products is important.</p>","PeriodicalId":23810,"journal":{"name":"Yakugaku zasshi : Journal of the Pharmaceutical Society of Japan","volume":"144 8","pages":"823-837"},"PeriodicalIF":0.3,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141861100","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 Functional Compounds Using Chemically Unstable Compounds Obtained from Medicinal Plants].","authors":"Seikou Nakamura","doi":"10.1248/yakushi.23-00161-1","DOIUrl":"10.1248/yakushi.23-00161-1","url":null,"abstract":"<p><p>Sulfur- or nitrogen-containing compounds from medicinal plants exhibit various biological activities such as anticancer potential. Developing efficient strategies to isolate or synthesize these compounds or their derivatives is a remarkable achievement. We have isolated several sulfur-containing compounds such as tetrahydro-2H-difuro[3,2-b:2',3'-c]furan-5(5aH)-one derivatives from Allium plants. We have devised a unique approach for the rapid preparation of thiopyranones using the regioselective sequential double Diels-Alder reaction; we used a naturally-occurring chemically-unstable intermediate such as thioacrolein, which is produced from allicin, a major component in garlic. The cytotoxicity of the synthetic thiopyranones against cancer stem cells (CSCs) was equal to or higher than that of (Z)-ajoene, the reference compound.</p>","PeriodicalId":23810,"journal":{"name":"Yakugaku zasshi : Journal of the Pharmaceutical Society of Japan","volume":"144 1","pages":"21-26"},"PeriodicalIF":0.3,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139088684","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}