Pub Date : 2024-01-01DOI: 10.1248/yakushi.23-00197-F
Seiji Komeda, Shin Aoki
{"title":"[Metals and Microorganisms: Expansion to Drug-discovery and Environmental Science].","authors":"Seiji Komeda, Shin Aoki","doi":"10.1248/yakushi.23-00197-F","DOIUrl":"https://doi.org/10.1248/yakushi.23-00197-F","url":null,"abstract":"","PeriodicalId":23810,"journal":{"name":"Yakugaku zasshi : Journal of the Pharmaceutical Society of Japan","volume":null,"pages":null},"PeriodicalIF":0.3,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141200713","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}
Pub Date : 2024-01-01DOI: 10.1248/yakushi.23-00172-1
Motohiro Sato
As populations grow older, the sustainability of current healthcare systems is being questioned. This paper considers what is necessary to ensure the sustainability of the healthcare system in Japan from the perspective of economics and public finance. In particular, it addresses the cost-effective use of limited medical resources. It also considers the problems of current regulations and regulatory regimes, which tend to protect vested interests. It may be necessary to carry out fundamental reforms of the regulatory system to deliver a sustainable healthcare system.
{"title":"[Challenges of Delivering Healthcare from an Economic and Public Finance Perspective].","authors":"Motohiro Sato","doi":"10.1248/yakushi.23-00172-1","DOIUrl":"10.1248/yakushi.23-00172-1","url":null,"abstract":"<p><p>As populations grow older, the sustainability of current healthcare systems is being questioned. This paper considers what is necessary to ensure the sustainability of the healthcare system in Japan from the perspective of economics and public finance. In particular, it addresses the cost-effective use of limited medical resources. It also considers the problems of current regulations and regulatory regimes, which tend to protect vested interests. It may be necessary to carry out fundamental reforms of the regulatory system to deliver a sustainable healthcare system.</p>","PeriodicalId":23810,"journal":{"name":"Yakugaku zasshi : Journal of the Pharmaceutical Society of Japan","volume":null,"pages":null},"PeriodicalIF":0.3,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141200643","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}
NMR is well known as one of the most important methods for elucidating the structure of organic compounds. Furthermore, it has recently been recognized as a powerful tool for quantitative analysis. The quantitative NMR (qNMR) has become an official analytical method described in detail in the Japanese Pharmacopoeia. And today, it is widely applied in drug development. The qNMR method offers many new advantages over traditional and conventional quantitative analysis methods. For example, this method requires only a few milligrams of the analyte and allows absolute quantitation of the analyte without using a qualified reference standard as a control sample. Then, it can be easily applied to most chemicals without expending significant time and resources on method development. In addition, residual solvent can be determined using qNMR methods. The peak area of an NMR spectrum is directly proportional to the number of protons contributing to the resonance. Based on this principle, the residual solvent can be determined by counting the signal corresponding to the residual solvent in the sample solution. We have applied qNMR as an alternative to GC. Thus, qNMR is an innovative and promising analytical technique that is expected to make significant progress in the future. Recently, the analytical research and quality control departments have been working together to expand this technology to a wide range of areas in the pharmaceutical industry.
{"title":"[The Applications of qNMR in Drug Quality Control].","authors":"Eri Ena, Yumi Asai, Takashi Hasebe, Hiroshi Oe, Shuichi Hirose, Yoshimasa Takahashi","doi":"10.1248/yakushi.23-00151-6","DOIUrl":"10.1248/yakushi.23-00151-6","url":null,"abstract":"<p><p>NMR is well known as one of the most important methods for elucidating the structure of organic compounds. Furthermore, it has recently been recognized as a powerful tool for quantitative analysis. The quantitative NMR (qNMR) has become an official analytical method described in detail in the Japanese Pharmacopoeia. And today, it is widely applied in drug development. The qNMR method offers many new advantages over traditional and conventional quantitative analysis methods. For example, this method requires only a few milligrams of the analyte and allows absolute quantitation of the analyte without using a qualified reference standard as a control sample. Then, it can be easily applied to most chemicals without expending significant time and resources on method development. In addition, residual solvent can be determined using qNMR methods. The peak area of an NMR spectrum is directly proportional to the number of protons contributing to the resonance. Based on this principle, the residual solvent can be determined by counting the signal corresponding to the residual solvent in the sample solution. We have applied qNMR as an alternative to GC. Thus, qNMR is an innovative and promising analytical technique that is expected to make significant progress in the future. Recently, the analytical research and quality control departments have been working together to expand this technology to a wide range of areas in the pharmaceutical industry.</p>","PeriodicalId":23810,"journal":{"name":"Yakugaku zasshi : Journal of the Pharmaceutical Society of Japan","volume":null,"pages":null},"PeriodicalIF":0.3,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140332027","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}
Pub Date : 2024-01-01DOI: 10.1248/yakushi.23-00156
Tomoko Ooshima, Tsuyoshi Kawakami
Tris(1-aziridinyl)phosphine oxide (APO) used as flame retardant in textile products, such as curtains, carpets, and sleeping clothes, is prohibited in Japan under the "Act on the Control of Household Products Containing Harmful Substances." This study developed a GC-MS-based method to quantify APO more accurately and safely than the current official method. The APO in textile products was extracted with methanol, the extract was replaced with acetone instead of hexane as previously reported, and purified by florisil cartridge column. This cleanup method was instead of the harmful and carcinogenic dichloromethane used for open column to purify the sample in the official method, giving consideration to health of analysts. For accurate and sensitive quantification, deuterated compound, APO-d12, was used as a surrogate standard. The calibration curve displayed linearity within the 0.01-2.0 µg/mL range for APO. The detection limit for APO was 0.008 µg/g with S/N=5, which was 50 times more sensitive than the current detection limit of 0.4 µg/g, enabling the analysis of sufficiently low concentrations. The recoveries in non-treatment cloth and flame-retardant textiles were 73.5-126.6% and relative standard deviations were 3.3-24.6% when 2 µg APO was added to 0.5 g of samples, confirming that it can be analyzed satisfactorily. Thus, the developed method is applicable to textile products of various materials.
{"title":"[GC-MS Analysis of Tris(1-aziridinyl)phosphine Oxide Flame Retardants in Textile Products].","authors":"Tomoko Ooshima, Tsuyoshi Kawakami","doi":"10.1248/yakushi.23-00156","DOIUrl":"10.1248/yakushi.23-00156","url":null,"abstract":"<p><p>Tris(1-aziridinyl)phosphine oxide (APO) used as flame retardant in textile products, such as curtains, carpets, and sleeping clothes, is prohibited in Japan under the \"Act on the Control of Household Products Containing Harmful Substances.\" This study developed a GC-MS-based method to quantify APO more accurately and safely than the current official method. The APO in textile products was extracted with methanol, the extract was replaced with acetone instead of hexane as previously reported, and purified by florisil cartridge column. This cleanup method was instead of the harmful and carcinogenic dichloromethane used for open column to purify the sample in the official method, giving consideration to health of analysts. For accurate and sensitive quantification, deuterated compound, APO-d<sub>12</sub>, was used as a surrogate standard. The calibration curve displayed linearity within the 0.01-2.0 µg/mL range for APO. The detection limit for APO was 0.008 µg/g with S/N=5, which was 50 times more sensitive than the current detection limit of 0.4 µg/g, enabling the analysis of sufficiently low concentrations. The recoveries in non-treatment cloth and flame-retardant textiles were 73.5-126.6% and relative standard deviations were 3.3-24.6% when 2 µg APO was added to 0.5 g of samples, confirming that it can be analyzed satisfactorily. Thus, the developed method is applicable to textile products of various materials.</p>","PeriodicalId":23810,"journal":{"name":"Yakugaku zasshi : Journal of the Pharmaceutical Society of Japan","volume":null,"pages":null},"PeriodicalIF":0.3,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139088699","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}
Pub Date : 2024-01-01DOI: 10.1248/yakushi.23-00166
Tetsuro Urushidani
In 1985, I was accepted as postdoc by Professor Forte of UC Berkeley. He discovered H+,K+-ATPase and established the membrane recycling theory as the activation mechanism for acid secretion using whole animals. H+,K+-ATPase is an enzyme that exchanges H+ with K+. In resting state, it locates on the tubulovesicles and the pump does not work because the membrane lacks K+ permeability. Upon stimulation, the tubulovesicles fuse to the apical membrane and acquire K+ permeability, turning the pump on. The main route was known to be protein kinase A (PKA), but its specific targets remained unknown. Right after I joined Forte's lab, I was fortunate enough to reproduce the above mechanism in vitro, and I discovered proteins of molecular weight 120 kDa and 80 kDa that were specifically phosphorylated in stimulated parietal cells. After I returned to Japan, the former was cloned and named as parchorin, which is one of the chloride intracellular channels. Although no progress was made on ezrin, I found out the importance of PIP2 and Arf6 using permeabilized gland models. After I left parietal cell research, the link between ezrin and Arf6 was revealed. PKA phosphorylates S66 of ezrin and also MST4. The former changes the N-terminal structure of ezrin to bind syntaxin3, and the latter phosphorylates ACAP4, an Arf6-GAP, to accelerate binding to ezrin. Subsequently, H+,K+-ATPase, SNAREs, ezrin, and Arf6-GAP are aligned on the apical membrane. However, there are still many unsolved questions and the intracellular mechanism of parietal cells remains an attractive research area.
{"title":"[Intracellular Mechanism of Gastric Acid Secretion: What is the True Switch?]","authors":"Tetsuro Urushidani","doi":"10.1248/yakushi.23-00166","DOIUrl":"10.1248/yakushi.23-00166","url":null,"abstract":"<p><p>In 1985, I was accepted as postdoc by Professor Forte of UC Berkeley. He discovered H<sup>+</sup>,K<sup>+</sup>-ATPase and established the membrane recycling theory as the activation mechanism for acid secretion using whole animals. H<sup>+</sup>,K<sup>+</sup>-ATPase is an enzyme that exchanges H<sup>+</sup> with K<sup>+</sup>. In resting state, it locates on the tubulovesicles and the pump does not work because the membrane lacks K<sup>+</sup> permeability. Upon stimulation, the tubulovesicles fuse to the apical membrane and acquire K<sup>+</sup> permeability, turning the pump on. The main route was known to be protein kinase A (PKA), but its specific targets remained unknown. Right after I joined Forte's lab, I was fortunate enough to reproduce the above mechanism in vitro, and I discovered proteins of molecular weight 120 kDa and 80 kDa that were specifically phosphorylated in stimulated parietal cells. After I returned to Japan, the former was cloned and named as parchorin, which is one of the chloride intracellular channels. Although no progress was made on ezrin, I found out the importance of PIP<sub>2</sub> and Arf6 using permeabilized gland models. After I left parietal cell research, the link between ezrin and Arf6 was revealed. PKA phosphorylates S66 of ezrin and also MST4. The former changes the N-terminal structure of ezrin to bind syntaxin3, and the latter phosphorylates ACAP4, an Arf6-GAP, to accelerate binding to ezrin. Subsequently, H<sup>+</sup>,K<sup>+</sup>-ATPase, SNAREs, ezrin, and Arf6-GAP are aligned on the apical membrane. However, there are still many unsolved questions and the intracellular mechanism of parietal cells remains an attractive research area.</p>","PeriodicalId":23810,"journal":{"name":"Yakugaku zasshi : Journal of the Pharmaceutical Society of Japan","volume":null,"pages":null},"PeriodicalIF":0.3,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139088700","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}
Pub Date : 2024-01-01DOI: 10.1248/yakushi.23-00162-1
Takashi Toyama, Runa Kudo, Yoshiro Saito
Methylmercury is a ubiquitous neurotoxic substance present in the environment, and health concerns, especially through the consumption of seafood, remain. Glutathione (GSH)-mediated detoxification and the excretion of methylmercury are known metabolic detoxification pathways. We have also discovered a mechanism by which endogenous super-sulfides convert methylmercury to nontoxic metabolites such as bis-methylmercury sulfide. However, these metabolites are present in very small quantities, and the significance of the detoxification of methylmercury by super-sulfides is not well understood. Methylmercury binds to thiol groups in vivo but can also react with highly reactive selenols (selenocysteine residues). Such covalent bonds (S-mercuration and Se-mercuration) are broken by nucleophilic substitution reactions with other thiol and selenols, however, the contribution of super-sulfides to this substitution reaction is not well understood. Interestingly, a recent study suggested that selenoprotein P, the major selenium transport protein in plasma, binds to methylmercury, however, Se-mercuration was not determined. In this review, we introduce these series of reactions and discuss their involvement with super-sulfides in methylmercury toxicity.
甲基汞是一种普遍存在于环境中的神经毒性物质,其健康问题,尤其是通过食用海产品引起的健康问题仍然存在。谷胱甘肽(GSH)介导的解毒和甲基汞的排泄是已知的代谢解毒途径。我们还发现了内源性超硫化物将甲基汞转化为双甲基硫化汞等无毒代谢物的机制。然而,这些代谢物的含量非常小,而且人们对超硫化物对甲基汞解毒的意义还不甚了解。甲基汞在体内会与硫醇基团结合,但也会与高活性硒醇(硒代半胱氨酸残基)发生反应。这种共价键(S-巯基化和 Se-巯基化)会通过与其他硫醇和硒醇的亲核置换反应而断裂,然而,人们对超硫化物在这种置换反应中的作用还不甚了解。有趣的是,最近的一项研究表明,血浆中主要的硒转运蛋白硒蛋白 P 可与甲基汞结合,但硒化作用并未确定。在本综述中,我们将介绍这一系列反应,并讨论它们与超硫化物在甲基汞毒性中的关系。
{"title":"[The Role of Supersulfide in Methylmercury Detoxification].","authors":"Takashi Toyama, Runa Kudo, Yoshiro Saito","doi":"10.1248/yakushi.23-00162-1","DOIUrl":"10.1248/yakushi.23-00162-1","url":null,"abstract":"<p><p>Methylmercury is a ubiquitous neurotoxic substance present in the environment, and health concerns, especially through the consumption of seafood, remain. Glutathione (GSH)-mediated detoxification and the excretion of methylmercury are known metabolic detoxification pathways. We have also discovered a mechanism by which endogenous super-sulfides convert methylmercury to nontoxic metabolites such as bis-methylmercury sulfide. However, these metabolites are present in very small quantities, and the significance of the detoxification of methylmercury by super-sulfides is not well understood. Methylmercury binds to thiol groups in vivo but can also react with highly reactive selenols (selenocysteine residues). Such covalent bonds (S-mercuration and Se-mercuration) are broken by nucleophilic substitution reactions with other thiol and selenols, however, the contribution of super-sulfides to this substitution reaction is not well understood. Interestingly, a recent study suggested that selenoprotein P, the major selenium transport protein in plasma, binds to methylmercury, however, Se-mercuration was not determined. In this review, we introduce these series of reactions and discuss their involvement with super-sulfides in methylmercury toxicity.</p>","PeriodicalId":23810,"journal":{"name":"Yakugaku zasshi : Journal of the Pharmaceutical Society of Japan","volume":null,"pages":null},"PeriodicalIF":0.3,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139088709","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}
Pub Date : 2024-01-01DOI: 10.1248/yakushi.23-00129
Yasuyuki Sadzuka
Liposomes have been reported to be useful nanocarrier, however, there are number of challenges to resolve before they can be optimized for drug delivery. Liposomes are taken up by cell in the reticuloendothelial system (RES). Polyethyleneglycol (PEG) modification on the liposomal membrane forms a fixed aqueous layer and thus prevents uptake by the RES. The physicochemical properties of liposomes that are most commonly evaluated particle size and zeta potential are not sufficient indicator of the passive targeting effect by PEG modification. In contrast, the fixed aqueous layer thickness (FALT) around liposomal surface was clear to be regulated to be the utilized action in the body. It was showed that the FALT value of PEG-modified liposomes containing doxorubicin increased with the increase in the molecular weight of PEG. Furthermore, PEG modification with a combination of high- and low- molecular weight PEGs on liposomal membranes showed in optimal results with respect to FALT and a higher antitumor effect. In addition, we designed and synthesized a novel PEG-lipid, different double arms PEG (DDA-PEG), which consisted of two PEG chains of 500 and 2000 in one molecule to develop more useful PEG-modified liposomes. DDA-PEG was found to have superior antitumor activity and was associated with the prevention of tumor metastasis. Furthermore, we sought to (-)-epigallocatechin-3-O-gallate (EGCG) functions as a target ligand of the 67-kDa laminin receptor (67LR), which is expressed on high-grade tumor cells. EGCG-PEG-modified liposome appear to have superior antitumor activity against high 67LR-expressing tumor cells, as the liposomes had dual effects.
{"title":"[To Assess Drug Delivery System Nanocarrier at Industrial Production: Establishment of Liposomal Surface Using Physicochemical Properties].","authors":"Yasuyuki Sadzuka","doi":"10.1248/yakushi.23-00129","DOIUrl":"10.1248/yakushi.23-00129","url":null,"abstract":"<p><p>Liposomes have been reported to be useful nanocarrier, however, there are number of challenges to resolve before they can be optimized for drug delivery. Liposomes are taken up by cell in the reticuloendothelial system (RES). Polyethyleneglycol (PEG) modification on the liposomal membrane forms a fixed aqueous layer and thus prevents uptake by the RES. The physicochemical properties of liposomes that are most commonly evaluated particle size and zeta potential are not sufficient indicator of the passive targeting effect by PEG modification. In contrast, the fixed aqueous layer thickness (FALT) around liposomal surface was clear to be regulated to be the utilized action in the body. It was showed that the FALT value of PEG-modified liposomes containing doxorubicin increased with the increase in the molecular weight of PEG. Furthermore, PEG modification with a combination of high- and low- molecular weight PEGs on liposomal membranes showed in optimal results with respect to FALT and a higher antitumor effect. In addition, we designed and synthesized a novel PEG-lipid, different double arms PEG (DDA-PEG), which consisted of two PEG chains of 500 and 2000 in one molecule to develop more useful PEG-modified liposomes. DDA-PEG was found to have superior antitumor activity and was associated with the prevention of tumor metastasis. Furthermore, we sought to (-)-epigallocatechin-3-O-gallate (EGCG) functions as a target ligand of the 67-kDa laminin receptor (67LR), which is expressed on high-grade tumor cells. EGCG-PEG-modified liposome appear to have superior antitumor activity against high 67LR-expressing tumor cells, as the liposomes had dual effects.</p>","PeriodicalId":23810,"journal":{"name":"Yakugaku zasshi : Journal of the Pharmaceutical Society of Japan","volume":null,"pages":null},"PeriodicalIF":0.3,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139088710","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}
An overwhelming surge of information regarding preparedness for postvaccination side effects had caused widespread confusion approximately since April 2021, when the coronavirus disease 2019 (COVID-19) vaccination had started for the general population in Japan. Notably, this resulted in a remarkably increased shortage of OTC acetaminophen formulations. The aim of this study was to elucidate the actual responses of the public in such an environment, how individuals acquired and understood information related to the management of postvaccination side effects, and how they obtained and used antipyretic analgesics before and after COVID-19 vaccination. We conducted a web-based survey in January 2022, targeting 400 individuals aged ≥20 years, who had received two COVID-19 vaccine doses, and excluded qualified professionals such as physicians and pharmacists. The results revealed that 67% of the respondents had obtained antipyretic analgesics in anticipation of adverse effects after vaccination, whereas 38% had taken these medicines before and/or after the second vaccination. Possible misappropriation of medicines from others, preventive administration, and lack of dosage and administration confirmation are the problems identified in medication acquisition and usage. Additionally, avoidance of antipyretic analgesics based on information without scientific evidence was observed. This study revealed no small amount of inappropriate use of medicines in situations, such as the COVID-19 pandemic, where there is an "infodemic" of mixed-quality information. Pharmacists, as experts in medication, should play a crucial role in promoting appropriate medication usage by consistently staying updated with the latest scientific evidence and proactively supporting OTC drug selection and counseling medication.
{"title":"[Actual Access and Usage of Antipyretic Analgesics before and after COVID-19 Vaccination: Pharmacist's Roles in Promoting Proper Use of Medicines during the Infodemic].","authors":"Kyoko Izumisawa, Natsuyo Yanagi, Hiroki Satoh, Yasufumi Sawada","doi":"10.1248/yakushi.23-00183","DOIUrl":"10.1248/yakushi.23-00183","url":null,"abstract":"<p><p>An overwhelming surge of information regarding preparedness for postvaccination side effects had caused widespread confusion approximately since April 2021, when the coronavirus disease 2019 (COVID-19) vaccination had started for the general population in Japan. Notably, this resulted in a remarkably increased shortage of OTC acetaminophen formulations. The aim of this study was to elucidate the actual responses of the public in such an environment, how individuals acquired and understood information related to the management of postvaccination side effects, and how they obtained and used antipyretic analgesics before and after COVID-19 vaccination. We conducted a web-based survey in January 2022, targeting 400 individuals aged ≥20 years, who had received two COVID-19 vaccine doses, and excluded qualified professionals such as physicians and pharmacists. The results revealed that 67% of the respondents had obtained antipyretic analgesics in anticipation of adverse effects after vaccination, whereas 38% had taken these medicines before and/or after the second vaccination. Possible misappropriation of medicines from others, preventive administration, and lack of dosage and administration confirmation are the problems identified in medication acquisition and usage. Additionally, avoidance of antipyretic analgesics based on information without scientific evidence was observed. This study revealed no small amount of inappropriate use of medicines in situations, such as the COVID-19 pandemic, where there is an \"infodemic\" of mixed-quality information. Pharmacists, as experts in medication, should play a crucial role in promoting appropriate medication usage by consistently staying updated with the latest scientific evidence and proactively supporting OTC drug selection and counseling medication.</p>","PeriodicalId":23810,"journal":{"name":"Yakugaku zasshi : Journal of the Pharmaceutical Society of Japan","volume":null,"pages":null},"PeriodicalIF":0.3,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141471154","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}
Pub Date : 2024-01-01DOI: 10.1248/yakushi.24-00095
Keisuke Yoshida
This review describes novel organocatalytic methods for the enantioselective construction of spiroindans and spirochromans and the application of the methods to the total synthesis of natural products. We developed an intramolecular Friedel-Craftstype 1,4-addition in which the substrates were a resorcinol derivative and 2-cyclohexenone linked by an alkyl chain. The reaction proceeded smoothly in the presence of a cinchonidine-based primary amine (30 mol%) with water and p-bromophenol as additives. A variety of spiroindanes were obtained with high enantioselectivity under these conditions. The reaction was applied in the first total synthesis of the unusual proaporphine alkaloid (-)-misramine, which included the key steps of enantioselective spirocyclization and double reductive amination of the keto-aldehyde to form a piperidine ring toward the end of the synthesis. The total synthesis of misrametine was achieved by selective demethylation of the methoxy group from the precursor to misramine. Next, a method for highly enantioselective organocatalytic construction of spirochromans containing a tetrasubstituted stereocenter was developed. An intramolecular oxy-Michael addition was catalyzed by a bifunctional cinchona alkaloid thiourea catalyst. A variety of spirochroman compounds containing a tetrasubstituted stereocenter were obtained with excellent enantioselectivity of up to 99% enantiomeric excess. The reaction was applied to the asymmetric formal synthesis of (-)-(R)-cordiachromene.
{"title":"[Development of Organocatalytic Reactions for the Synthesis of Natural Products and Pharmaceuticals].","authors":"Keisuke Yoshida","doi":"10.1248/yakushi.24-00095","DOIUrl":"https://doi.org/10.1248/yakushi.24-00095","url":null,"abstract":"<p><p>This review describes novel organocatalytic methods for the enantioselective construction of spiroindans and spirochromans and the application of the methods to the total synthesis of natural products. We developed an intramolecular Friedel-Craftstype 1,4-addition in which the substrates were a resorcinol derivative and 2-cyclohexenone linked by an alkyl chain. The reaction proceeded smoothly in the presence of a cinchonidine-based primary amine (30 mol%) with water and p-bromophenol as additives. A variety of spiroindanes were obtained with high enantioselectivity under these conditions. The reaction was applied in the first total synthesis of the unusual proaporphine alkaloid (-)-misramine, which included the key steps of enantioselective spirocyclization and double reductive amination of the keto-aldehyde to form a piperidine ring toward the end of the synthesis. The total synthesis of misrametine was achieved by selective demethylation of the methoxy group from the precursor to misramine. Next, a method for highly enantioselective organocatalytic construction of spirochromans containing a tetrasubstituted stereocenter was developed. An intramolecular oxy-Michael addition was catalyzed by a bifunctional cinchona alkaloid thiourea catalyst. A variety of spirochroman compounds containing a tetrasubstituted stereocenter were obtained with excellent enantioselectivity of up to 99% enantiomeric excess. The reaction was applied to the asymmetric formal synthesis of (-)-(R)-cordiachromene.</p>","PeriodicalId":23810,"journal":{"name":"Yakugaku zasshi : Journal of the Pharmaceutical Society of Japan","volume":null,"pages":null},"PeriodicalIF":0.3,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141861098","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}
Pub Date : 2024-01-01DOI: 10.1248/yakushi.24-00091
Atsushi Sawamoto
Adipose tissue plays a central metabolic role in systemic energy metabolism via nutrient exchange and secretion of adipose-derived hormones and cytokines. Adipose tissue dysfunction increases the risk of developing conditions, including type 2 diabetes, coronary artery disease, stroke, and cancer, ultimately shortening healthy lifespan. Maintaining adipose tissue functions has recently garnered attention as a means to extend healthy life expectancy. We previously developed a T-cell activation-inhibitory assay, which facilitates efficient selection of candidate substances for extending healthy lifespan. Using this assay, we identified two candidate substances: Cynandione A (CA), a major component of Cynanchum wilfordii, and N-caffeoyltryptophan (NCT) found in coffee. This review summarizes recent findings regarding the effect of CA and NCT on adipocyte (the primary cells in adipose tissue) function, and their potential contribution to extending healthy life expectancy.
脂肪组织通过营养交换和分泌脂肪源性荷尔蒙和细胞因子,在全身能量代谢中发挥着核心代谢作用。脂肪组织功能障碍会增加罹患各种疾病的风险,包括 2 型糖尿病、冠状动脉疾病、中风和癌症,最终缩短健康寿命。保持脂肪组织功能作为延长健康寿命的一种手段,最近引起了人们的关注。我们之前开发了一种 T 细胞活化抑制试验,有助于有效筛选出延长健康寿命的候选物质。利用这种检测方法,我们确定了两种候选物质:咖啡中的 N-咖啡酰色氨酸(NCT)。本综述总结了有关 CA 和 NCT 对脂肪细胞(脂肪组织中的初级细胞)功能影响的最新发现,以及它们对延长健康预期寿命的潜在贡献。
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