著者
朝比奈 泰子 堀 里子 澤田 康文
出版者
公益社団法人 日本薬学会
雑誌
YAKUGAKU ZASSHI (ISSN:00316903)
巻号頁・発行日
vol.130, no.2, pp.271-275, 2010-02-01 (Released:2010-02-01)
参考文献数
25
被引用文献数
1

Hyperkalemia is common in patients with renal disease, and is sometimes caused by dietary potassium intake. We aimed to determine and compare the content of potassium in nine brands of glucosamine supplements sold in the Japanese market and via the Internet. The potassium content was 0.165-3 mg per daily dose in Japanese products, which contained glucosamine hydrochloride or N-acetylglucosamine, while the content in foreign products, in which glucosamine was sulfated, was 197-280 mg. Our results show that the potassium content in glucosamine sulfate supplements can correspond to 20% of the maximum daily intake of potassium by patients on hemodialysis, because the products sometimes contain glucosamine as glucosamine sulfate potassium chloride for stabilization. Although it is not permitted to sell glucosamine sulfate as food in Japan, consumers can easily buy foreign products that contain glucosamine sulfate via the Internet, and those products rarely indicate the potassium content. Health professionals should pay attention to patients' use of glucosamine supplements, especially when patients' dietary potassium intake needs to be restricted.
著者
安原 眞人
出版者
公益社団法人 日本薬学会
雑誌
YAKUGAKU ZASSHI (ISSN:00316903)
巻号頁・発行日
vol.142, no.9, pp.929-935, 2022-09-01 (Released:2022-09-01)
参考文献数
11

In order to provide sustainable medical care in a super-aging society, pharmacists are required to play a role in integrated community care systems in cooperation with multiple professionals, in addition to prescription-based dispensing. We propose the necessity of building an interprofessional information sharing system, lifelong training for pharmacists, and the establishment of a professional certification system.
著者
山本 信夫
出版者
公益社団法人 日本薬学会
雑誌
YAKUGAKU ZASSHI (ISSN:00316903)
巻号頁・発行日
vol.142, no.9, pp.951-963, 2022-09-01 (Released:2022-09-01)
参考文献数
4
被引用文献数
2

The anticipation of Japan's decreased birthrate and a shift to an aged society has led to the field of medical care to review the country's social security system. The review calls for a reform of the medical insurance system under the universal health coverage system to fit the changing demographic. The target year of 2025 has the government advocating for an “integrated community care system”, with the ‘baby-boom generation’ turning 75. This is a sustainable regional system that can cope with the aging society and the declining birthrate simultaneously. Within this new system, I would like to discuss The Strategic Plan of the Japan Pharmaceutical Association, released with the aim of realizing pharmacists and pharmacy services that can immediately respond to the expectations of society; from the perspective of the theme of this symposium, “Communicating the image of pharmacists in a community-based society”.
著者
南郷 大輔 関塚 大 五島 誠 越前 宏俊
出版者
公益社団法人 日本薬学会
雑誌
YAKUGAKU ZASSHI (ISSN:00316903)
巻号頁・発行日
vol.142, no.4, pp.341-344, 2022-04-01 (Released:2022-04-01)
参考文献数
15

Nowadays, medical big data has been developed and made available in a variety of fields such as epidemiology and pharmacovigilance. Spontaneous reporting databases are one category of medical big data and that has been adequate for analysing events related to side effects that rarely occur in general practice. These data are freely available in several countries. In Japan, the Pharmaceuticals and Medical Devices Agency has developed the Japanese Adverse Drug Event Report (JADER), and the Food and Drug Administration (FDA) developed the FDA Adverse Events Reporting System (FAERS) in the United States. Since the release of these medical big data, many researchers in academic and research setting have accessed them, but it is still difficult for many medical professionals to analyse these data due to costs and operation of requisite statistical software. In this section, we give some tips to study spontaneous reporting databases resulting from our learning experiences.
著者
齋藤 百枝美 野舘 敬直 丸山 桂司 土屋 雅勇 渡邊 真知子 丹羽 真一
出版者
公益社団法人 日本薬学会
雑誌
YAKUGAKU ZASSHI (ISSN:00316903)
巻号頁・発行日
vol.132, no.3, pp.369-379, 2012-03-01 (Released:2012-03-01)
参考文献数
15
被引用文献数
3 3

We established a practical training program to nurture pharmacists who can give smoking cessation instructions. The program was provided to 85 interns (45 males and 40 females) in Teikyo University Hospital. The one-day practical training was provided to groups comprised of five members each. The training consisted of studies on the adverse effects of smoking, general outlines of the outpatient smoking cessation service, experiencing Smokerlyzer, studies about smoking-cessation drugs, studies about a smoking cessation therapy using cognitive-behavioral therapy and motivational interviewing, and case studies applying role-playing. Before and after the practical training, we conducted a questionnaire survey consisting of The Kano Test for Social Nicotine Dependence (KTSND) and the assessment of the smoking status, changes in attitudes to smoking, and willingness and confidence to give smoking cessation instructions. The overall KTSND score significantly dropped from 14.1±4.8 before the training to 8.9±4.8 after the training. The confidence to give smoking cessation instructions significantly increased from 3.4±1.9 to 6.2±1.3. Regarding the correlation between the smoking status and willingness and confidence to give smoking cessation instructions, the willingness and confidence were lower among the group of interns who either smoked or had smoked previously, suggesting that smoking had an adverse effect. A total of 88.2% of the interns answered that their attitudes to smoking had “changed slightly” or “changed” as a result of the training, indicating changes in their attitudes to smoking. Given the above, we believe that our newly-established smoking cessation instruction training is a useful educational tool.
著者
高橋 憲二 小島 健吾 中島 理恵 鈴木 達彦 渡邉 文之
出版者
公益社団法人 日本薬学会
雑誌
YAKUGAKU ZASSHI (ISSN:00316903)
巻号頁・発行日
pp.22-00079, (Released:2022-07-05)
参考文献数
38

Collaborations between hospital and community pharmacists play a key role in ensuring consistent continuation of pharmacotherapy within official medical care plans designed to promote community-based healthcare. A previous study conducted by the authors clarified the constructs of collaboration between the hospital and community pharmacists from the hospital pharmacist's perspective. In this study, a similar questionnaire was used to survey a group of pharmacies with 424 outlets nationwide, and 244 responses were collected. Factor analysis from the community pharmacists’ perspective extracted five latent factors comprising 18 variables, and structural equation modeling yielded a model with a high goodness-of-fit. In the latter model, variables representing “Organizational climate” and “Basic policy on collaboration” formed the foundation of the collaboration between hospital and community pharmacists, while variables representing “Understanding of healthcare policy,” “Resources for collaboration,” and “Community support systems” represented concepts that flexibly compensated for fluctuations in medical policy. These trends were similar to those of the constructs previously indicated by hospital pharmacists. We performed multiple regression analysis and structural equation modeling to confirm the impact of the inclusion of “Need for collaboration” as a dependent variable on the proposed constructs of hospital-community pharmacist collaboration using different analytical methods. Our results indicated that “Organizational climate,” “Basic policy on collaboration,” and “Community support systems” affected the “Need for collaboration”. Our findings indicate that future studies are needed to confirm and clarify the causal relationships demonstrated by the constructs of hospital-community pharmacist collaboration seen within the current study.
著者
平田 收正
出版者
公益社団法人 日本薬学会
雑誌
YAKUGAKU ZASSHI (ISSN:00316903)
巻号頁・発行日
vol.142, no.8, pp.829-836, 2022-08-01 (Released:2022-08-01)
参考文献数
9

The first-phase third-party accreditation conducted by the Japan Accreditation Board for Pharmaceutical Education between FY 2013 and 2019 revealed various issues regarding current pharmacy education programs. In addition, the report of the Ministry of Health, Labour and Welfare's Study Group on the Training and Quality Improvement of Pharmacists, which was published in 2021, identified a broad range of issues in pharmaceutical education related to pharmacist training and quality improvement. Many of these issues are concerned with university curricula; thus, in order to ensure and enhance the quality of pharmaceutical education and develop pharmaceutical human resources that society demands, it is extremely important for each university to improve its curricula. Since revision of the model core curriculum for pharmaceutical education is currently underway, in this symposium, we held a discussion to identify points that need to be improved regarding the current model core curriculum to ensure and enhance the quality of pharmaceutical education in light of the above-mentioned issues, and incorporate the corresponding measures into the basic policy for revision of the model core curriculum.
著者
合田 幸広
出版者
公益社団法人 日本薬学会
雑誌
YAKUGAKU ZASSHI (ISSN:00316903)
巻号頁・発行日
vol.134, no.2, pp.197-202, 2014-02-01 (Released:2014-02-01)
参考文献数
9
被引用文献数
1 1

With the prefectural governments' aid of the purchase, the Division of Pharmacognosy, Phytochemistry and Narcotics, National Institute of Health Sciences (NIHS) successively has surveyed illegal constituents in health food products implicitly advertizing tonic or slimming effect since the fiscal year of 2002 (slimming type) or 2003 (tonic type). The average numbers of the analyzed products per year are about 100 (slimming type) and 150 (tonic type), respectively. We also continuously distribute standards of authentic samples of several illegal components such as N-nitrosofenfluramine (NFF) and sildenafil (SIL) to prefectural institutes and the average gross number per year is about 140. In the case of slimming type, the fact that the products containing NFF were widely sold in Japanese markets in 2002 is well known. In addition, phenolphthalein, fenfluramine, sibtramine, desdimethylsibtramine, orlistat, mazindol, Rhubarb, Senna Leaf, etc. have been found as illegal constituents. In the tonic type products, we have identified more than 20 synthetic compounds relating to the erectile dysfunction (ED) treatment drugs, SIL, vardenafil and tadalafil (TDF). Since 2005, their synthetic intermediates and the patented but non-approved PDE5 inhibitors also have been found. It should be noted that TDF was found in the shells of capsule in 2009 and that mutaprodenafil was found as pro-drug type illegal component in 2010. In this report identification method of these illegal constituents is briefly described and then analytical trend in this decade is reviewed.
著者
小田口 浩 日向 須美子 関根 麻理子 中森 俊輔 竹元 裕明 黄 雪丹 大嶋 直浩 嶋田 典基 楊 金緯 天倉 吉章 日向 昌司 内山 奈穂子 小林 義典 袴塚 高志 合田 幸広 花輪 壽彦
出版者
公益社団法人 日本薬学会
雑誌
YAKUGAKU ZASSHI (ISSN:00316903)
巻号頁・発行日
vol.139, no.11, pp.1417-1425, 2019-11-01 (Released:2019-11-01)
参考文献数
21
被引用文献数
8 13

Ephedra Herb is defined in the 17th edition of the Japanese Pharmacopoeia (JP) as the terrestrial stem of Ephedra sinica Stapf., Ephedra intermedia Schrenk et C.A. Meyer, or Ephedra equisetina Bunge (Ephedraceae). The stems of Ephedra Herb contain greater than 0.7% ephedrine alkaloids (ephedrine and pseudoephedrine). Despite its high effectiveness, Ephedra Herb exert several adverse effects, including palpitation, excitation, insomnia, and dysuria. Both the primary and adverse effects of Ephedra Herb have been traditionally believed to be mediated by these ephedrine alkaloids. However, our study found that several pharmacological actions of Ephedra Herb were not associated with ephedrine alkaloids. We prepared an ephedrine alkaloid-free Ephedra Herb extract (EFE) by eliminating ephedrine alkaloids from Ephedra Herb extract (EHE) using ion-exchange column chromatography. EFE exerted analgesic, anti-influenza, and anticancer activities in the same manner as EHE. Moreover, EFE did not induce adverse effects due to ephedrine alkaloids, such as excitation, insomnia, and arrhythmias, and showed no toxicity. Furthermore, we evaluated the safety of EFE in healthy volunteers. The number of adverse event cases was higher in the EHE-treated group than in the EFE-treated group, although the difference was not significant. Our evidence suggested that EFE was safer than EHE.
著者
垣内 信子
出版者
公益社団法人 日本薬学会
雑誌
YAKUGAKU ZASSHI (ISSN:00316903)
巻号頁・発行日
vol.137, no.10, pp.1193-1200, 2017-10-01 (Released:2017-10-01)
参考文献数
44
被引用文献数
2

Although Kampo medicine is now fully integrated into the modern Japanese healthcare system, most Kampo formulations depend on imported crude drugs from limited foreign areas. To prepare for possible shortages of crude drugs in the future, a wider scope for the supply of medicinal plants is necessary. We conducted field research and collaborated with international laboratories for phylogenic analysis and evaluation of medicinal plant resources. Our research on ephedra plants from a wide region of Eurasia has, for example, confirmed their phylogenic structure: based on DNA sequencing analysis of nuclear ribosomal internal transcribed spacer region 1 (ITS1) as well as the chloroplast intergenic spacer between trnL and trnF (trnL-F), the 8 major Chinese species and related plants grown on the continent could be divided into 3 groups. Additionally, Ephredra sinica was found to be synonymous with Ephredra dahurica and was reduced to a subspecies of Ephredra distachya. Furthermore, Ephredra likiangensis and Ephredra gerardiana, which are grouped in separate phylogenic trees, would be good candidates for medicinal material. Aconites from Hokkaido, as an example of domestic plants reviewed, were collected for phylogenic and aconitine alkaloid content analysis. The phylogenic analysis of nr ITSs revealed that the majority of specimens were genetically similar. However, the aconitine alkaloid content of the tuberous roots demonstrated that specimens from different habitats had varying alkaloid profiles. Environmental pressure of each habitat is presumed to have caused the morphology and aconitine alkaloid profiles of these genetically similar specimens to diversify.
著者
上井 優一 鈴木 里彩 岩本 喜久生
出版者
公益社団法人 日本薬学会
雑誌
YAKUGAKU ZASSHI (ISSN:00316903)
巻号頁・発行日
vol.131, no.5, pp.853-861, 2011-05-01 (Released:2011-05-01)
参考文献数
28
被引用文献数
6 7

It is well known that nonsteroidal anti-inflammatory drugs (NSAIDs) affect the pharmacokinetics of methotrexate, but there are several reports showing negative consequences. In this study, we evaluated drug interactions by performing a meta-analysis on published data examining the effect of NSAIDs on pharmacokinetic parameters of methotrexate. The combined standardized mean difference of the maximum blood concentration after oral administration of methotrexate was calculated to be −0.00 (95% confidence interval, −0.30 to 0.30) based on 6 clinical trials, and there was no significant effect of NSAIDs (p=0.9967). However, it is also represented that the NSAIDs significantly increased the area under the blood concentration-time curve of methotrexate (combined standardized mean difference, 0.73; 95% confidence interval, 0.32 to 1.14; p=0.0004; 11 trials). Furthermore, the combined standardized mean differences in total and renal clearance of methotrexate were estimated to be −0.80 (95% confidence interval, −1.41 to −0.18; p=0.0109; 6 trials) and −0.76 (95% confidence interval, −1.40 to −0.11; p=0.0220; 11 trials), respectively, implying that NSAIDs interfere with urinary excretion of methotrexate. In conclusion, the integration of the published reports by these meta-analyses shows that NSAIDs increase blood levels of methotrexate by influencing renal excretion of the antifolate.
著者
富田 隆 後藤 英和 住谷 賢治 吉田 正 田中 勝也 幸田 幸直
出版者
公益社団法人 日本薬学会
雑誌
YAKUGAKU ZASSHI (ISSN:00316903)
巻号頁・発行日
vol.136, no.3, pp.517-521, 2016-03-01 (Released:2016-03-01)
参考文献数
9
被引用文献数
2 4

To avoid fluctuation of the serum lithium concentration (CLi), sodium chloride (NaCl) intake was regulated in oral alimentation. A 62-year-old woman was hospitalized and orally administered 400 mg of lithium carbonate a day to treat her mania. Her CLi was found to be 0.75-0.81 mEq/L. Vomiting made it difficult for the patient to ingest meals orally, and therefore parenteral nutrition with additional oral intake of protein-fortified food was initiated. On day 22, parenteral nutrition was switched to oral alimentation to enable oral intake of food. The total NaCl equivalent amount was decreased to 1.2 g/d, and the CLi increased to 1.15 mEq/L on day 26. Oral alimentation with semi-solid food blended in a mixer was immediately initiated. Although the total NaCl equivalent amount was increased to 4.5-5.0 g/d, her CLi remained high at 1.14-1.17 mEq/L on days 33 and 49, respectively. We investigated oral administration of NaCl (1.8 g/d) on day 52. The total NaCl equivalent amount was increased to 6.3-6.8 g/d, and the CLi decreased to 1.08-0.97 mEq/L on days 63 and 104, respectively. After the start of the orally administered NaCl, her diet was changed to a completely blended diet on day 125. The total NaCl equivalent amount was increased to 9.0-14.5 g/d, and the CLi decreased to 0.53 mEq/L on day 152; therefore, the oral administration of NaCl was discontinued on day 166. The CLi was found to be 0.70-0.85 mEq/L on days 176 and 220.
著者
加藤 信太郎 齋藤 佳敬 小野田 紘子 熊井 正貴 今井 俊吾 敦賀 健吉 武隈 洋 菅原 満
出版者
公益社団法人 日本薬学会
雑誌
YAKUGAKU ZASSHI (ISSN:00316903)
巻号頁・発行日
vol.142, no.7, pp.755-760, 2022-07-01 (Released:2022-07-01)
参考文献数
19
被引用文献数
1

Naldemedine (Nal) is widely used as a therapeutic drug against opioid-induced constipation. However, patients in phase III trials are limited to those with good performance status (PS). Cancer patients may have inferior PS owing to progression of symptoms and adverse events from chemotherapy. Therefore, it is important to survey the efficacy of Nal in patients with poor PS. This study aimed to evaluate Nal efficacy in patients with poor PS. We retrospectively investigated patients from July 2017 to June 2019 and compared Nal efficacy between patients with good and poor PS. The efficacy of Nal was evaluated using changes in the number of spontaneous bowel movements 7 days before and after the introduction of Nal with reference to previous reports. Multivariate analysis was performed to reveal whether poor PS affects Nal efficacy. In total, 141 patients at the Hokkaido University Hospital were analyzed. The effective rate of Nal from day 1 to day 7 of administration was 71.7% and 71.4% in the patients with good and poor PS, respectively, that from day 1 to day 2 of administration was 61.1% and 57.1%, respectively, and that from day 3 to day 7 of administration was 60.2% and 71.4%, respectively, suggesting an absence of significant differences. Furthermore, results of multivariate analysis showed that “best supportive care” and “body weight (55 kg and above)” reduced Nal efficacy. In conclusion, Nal showed similar effectiveness in patients with poor PS as that in those with good PS.
著者
内山 奈穂子 花尻(木倉) 瑠理 正田 卓司 福原 潔 合田 幸広
出版者
公益社団法人 日本薬学会
雑誌
YAKUGAKU ZASSHI (ISSN:00316903)
巻号頁・発行日
vol.131, no.7, pp.1141-1147, 2011-07-01 (Released:2011-07-01)
参考文献数
12
被引用文献数
11 12

Recently, many psychotropic herbal products, named such as “Spice”, were distributed worldwide via the Internet. In our previous study, several synthetic cannabinoids were identified as adulterants in herbal products being available in Japan due to their expected narcotic effects. Among those, two derivatives of Δ9-tetrahydrocannabinol (Δ9-THC), which is major psychotropic cannabinoid of marijuana, cannabicyclohexanol (CCH, 3-[2-hydroxy-4-(2-methylnonan-2-yl)phenyl]cyclohexan-1-ol) and CP-47,497 (3-[2-hydroxy-4-(2-methyloctan-2-yl)phenyl]cyclohexan-1-ol), have been controlled as designated substances (Shitei-Yakubutsu) under the Pharmaceutical Affairs Law since November 2009. CCH was detected together with its trans-form (1-epimer) in many herbal products, and CCH and CP-47,497 have two chiral centers in the structures. However, the pharmaceutical activities of the isomers of CCH have not been reported. This study presents chiral separations of CCH, its trans-form and CP-47,497 in the products using LC-circular dichroism (CD) and LC-MS analyses. The enantiomeric pairs of CCH, its trans-form and CP-47,497 were separated, respectively. Subsequently, the analyses of the herbal products showed that CCH and its trans-form existed as mixtures of enantiomers and the relative ratios of CCH and the trans-form enantiomers ranged from 42/58% to 53/47% and from 33/67% to 52/48%, respectively.
著者
鈴木 啓司 児玉 靖司 渡邉 正己
出版者
公益社団法人 日本薬学会
雑誌
YAKUGAKU ZASSHI (ISSN:00316903)
巻号頁・発行日
vol.126, no.10, pp.859-867, 2006-10-01 (Released:2006-10-01)
参考文献数
48
被引用文献数
6 6

Accumulated evidence has shown that exposure to low-dose radiation, especially doses less than 0.1 Gy, induces observable effects on mammalian cells. However, the underlying molecular mechanisms have not yet been clarified. Recently, it has been shown that low-dose radiation stimulates growth factor receptor, which results in a sequential activation of the mitogen-activated protein kinase pathway. In addition to the activation of the membrane-bound pathways, it is becoming evident that nuclear pathways are also activated by low-dose radiation. Ionizing radiation has detrimental effects on chromatin structure, since radiation-induced DNA double-strand breaks result in discontinuity of nucleosomes. Recently, it has been shown that ATM protein, the product of the ATM gene mutated in ataxia-telangiectasia, recognizes alteration in the chromatin structure, and it is activated through intermolecular autophosphorylation at serine 1981. Using antibodies against phosphorylated ATM, we found that the activated and phosphorylated ATM protein is detected as discrete foci in the nucleus between doses of 10 mGy and 1 Gy. Interestingly, the size of the foci induced by low-dose radiation was equivalent to the foci induced by high-dose radiation. These results indicate that the initial signal is amplified through foci growth, and cells evolve a system by which they can respond to a small number of DNA double-strand breaks. From these results, it can be concluded that low-dose radiation is sensed both in the membrane and in the nucleus, and activation of multiple signal transduction pathways could be involved in manifestations of low-dose effects.
著者
横山 晴子 山田 安彦 山村 喜一 中村 均 伊賀 立二
出版者
公益社団法人 日本薬学会
雑誌
YAKUGAKU ZASSHI (ISSN:00316903)
巻号頁・発行日
vol.121, no.3, pp.233-237, 2001-03-01 (Released:2002-09-27)
参考文献数
7
被引用文献数
13 11

The effect of mouth wash on the removal of drug residues in both mouth and pharynx after the use of fluticasone propionate dry powder inhaler (FP-DPI) was studied. The concentration of FP in mouth wash after sprinkle and inhalation of Flutide® 50, 100, 200 Rotadisk® was determined by HPLC-UV. The total amount of the removed FP was measured by the sum of the concentration of FP in 5 times of mouth washes. The mouth wash procedures removed totally 79.3±4.4% (50 μg), 68.5±3.6% (100 μg), 69.3±3.4% (200 μg) of sprinkled amount of FP and 29.5±11.1% (50 μg), 35.6±6.6% (100 μg), 31.6±8.3% (200 μg) of inhaled, respectively. It was required for the removal of 90% of the totally recovered FP to do two times of mouth washes in each case. These data suggest that the mouth wash is an effective precaution for candidiasis induced by FP delivered by DPI.
著者
此村 恵子 森井 康博 赤沢 学
出版者
公益社団法人 日本薬学会
雑誌
YAKUGAKU ZASSHI (ISSN:00316903)
巻号頁・発行日
vol.142, no.4, pp.413-420, 2022-04-01 (Released:2022-04-01)
参考文献数
17

Pharmacists play a key role in optimizing the safe and effective use of medicines in the super-aged society in Japan. Recently, community pharmacists' role has been transformed and expanded to provide patient-centered care. This study aimed to simulate a change in the demand for community pharmacists resulting from this shift in their role, from 2019 to 2035. The change in demand was estimated by the number of prescriptions obtained from publicly available sources of information. The number of required community pharmacists was calculated separately for full-time and part-time pharmacists and the pharmacists engaged in home medical care. This number was calculated using the estimated demand, the number of prescriptions dispensed per day, and annual working days. We evaluated the effect of changes in the working conditions, which include changes in the dispensing process time, rate of part-time staff and their work time, and number of home medical care per day, on the number of community pharmacists. When the number of prescriptions dispensed per day was set at 19.8, the demand for community pharmacists was estimated as 188,314 in 2035. Furthermore, due to the changes in the working conditions, the demand is expected to change from 153,362 to 266,944. Although the increasing provision of drug information time leads to an increasing number of pharmacists, combining it with work efficiency services could prevent or decrease it. The optimal supply and demand balance of community pharmacists should be determined by both, promoting pharmaceutical care services and improving work efficiency.
著者
佐野 和憲
出版者
公益社団法人 日本薬学会
雑誌
YAKUGAKU ZASSHI (ISSN:00316903)
巻号頁・発行日
vol.139, no.7, pp.999-1005, 2019-07-01 (Released:2019-07-01)
参考文献数
14

Pathological α-synuclein (αSyn) has been shown to retain the ability to propagate as prions in humans and animals. However, the molecular basis underlying the prion-like properties of αSyn remains poorly understood. We examined whether brain tissues from cases of dementia with Lewy bodies (DLB), which contain serine 129 (Ser129)-phosphorylated insoluble aggregates of αSyn, exhibit prion-like seeding activity in vitro using the real-time quaking-induced conversion (RT-QuIC) seeding assay. Brain tissues from cases of diffuse neocortical DLB yielded a 50% seeding dose of 107.3-109.8/g brain. The RT-QuIC assay could discriminate between DLB and other neurological and neurodegenerative disorders, suggesting its potential applicability for differential diagnosis. Insoluble aggregates of αSyn>250 kDa detected only in DLB brain tissues by Western blotting analysis were specifically phosphorylated at Ser129. Therefore, we postulated that Ser129-phosphorylated insoluble aggregates of αSyn have prion-like seeding activity. However, insoluble aggregates of recombinant human αSyn (rSyn) with increased β-sheet structures showed little seeding activity in either the phosphorylated or nonphosphorylated state. In contrast, prefibrillar oligomers of rSyn showed seeding activity both with and without phosphorylation. The findings of the present study suggested that soluble oligomeric αSyn, but not the fully fibrillary form, is a seeding species in vitro.
著者
青木 良子 佐井 君江 勝田 由紀子 鈴木 美佳 鈴木 康夫 石井 明子 斎藤 嘉朗
出版者
公益社団法人 日本薬学会
雑誌
YAKUGAKU ZASSHI (ISSN:00316903)
巻号頁・発行日
vol.142, no.5, pp.547-560, 2022-05-01 (Released:2022-05-01)
参考文献数
19
被引用文献数
1

Biosimilars are less expensive than their originators, and Japanese government policies call for their development and promotion. However, the adoption and prescription of some biosimilars, especially antibody/its-related ones, have been delayed for use in Japan, possibly due to concerns on the differences in quality attributes such as glycan structures between the originators and their biosimilars, and that clinical efficacy/safety studies are conducted for usually one disease and its results extrapolated to other indications. We conducted a questionnaire survey among physicians in four disease areas (hematology, medical oncology, rheumatoid arthritis, and inflammatory bowel disease), where biosimilars of antibody/its-related drugs have been approved, regarding their thoughts on the adoption and prescription of biosimilars in Japan from January to April 2020. We received totally 1024 responses. When adopting biosimilars and explaining them to patients, physicians requested specific information including the comparative results of phase III clinical trials and quality characteristics between biosimilars and their originators; the results of clinical studies on switching from originators to their biosimilars; and a comparison of the estimated cost on patients in consideration of the high medical cost payment system. Priority differed depending on the studied disease areas. In terms of post-marketing information, physicians requested a variety of information. When explaining biosimilars to the patients, physicians would like to use general material from government describing the comparability between originators and their biosimilars. These results suggest that physicians sought more comparative information on the quality, efficacy, and patients' cost between originators and their biosimilars when adopting or prescribing biosimilars.