著者

長野 晃三 長野 希美

出版者

公益社団法人日本薬学会

雑誌

藥學雜誌 (ISSN:00316903)

巻号頁・発行日

vol.117, no.10, pp.749-763, 1997-11-01

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Various experimental data have been supporting an idea that the conformation of A-site tRNA is different from that of P-site tRNA and have led to a new tRNA docking pair model, in which the highly conserved G18 and G19 of D-loop in A-site tRNA and C56 and C61 of TΨC-loop in P-site tRNA base pair exist along with the conventional base pairs of adjacent codon-anticodon interactions. This A-P tRNA pair model can be translocated to the P-E tRNA model without changing the conformation except the ACCA termini, keeping the position of the growing nascent polypeptide chain. On the other hand, it is noteworthy that C1378 of E. coli 16S rRNA cross-links to the 32 position on the anticodon loop of A-site tRNA in the pre-translocational state, and also to the same position of E-site tRNA in the post-translocational state, instead of the corresponding position of P-site tRNA. It resulted in a relationship between the A-P and P-E tRNA docking pair models in the pre- and post-translocational states, respectively, caused by a rotation with the angle of 25° around the axis of rotation symmetry. Furthermore, nucleotide sequence analysis showed that CGAGC1107 of 16S rRNA is complementary with the conserved GTΨCG57 of tRNA. When it is combined with the P-E tRNA pair model, the crystallograp-hically obtained L-shaped tRNA model fits both A-site codon with base pairings and the free TΨC-loop of P-site tRNA without base pairings. The base pairings between the GTΨCG57 of tRNA and the CGAGC1107 of 16S rRNA destabilize the bound aminoacyl-tRNA and result in a flow of discarding noncognate and near-cognate ternary complexes until cognate one arrives at the A-site codon. Recognition of a cognate ternary complex could occur, starting from breaking a hydrogen bond between N3 atom of U33 and O5' atom of A36 in the aminoacyl-tRNA, with base pairings of the codon-anticodon interactions, the conserved A 1394 in the 16S rRNA to the conserved U33 in the anticodon loop of the tRNA. The exposed U33 of the aminoacyl-tRNA is paired with A1394 in the recognitionmode of A site, and finally passed to A1398 of A-site tRNA in the A-P tRNA pair model of the pre-translocational state. The exposure of U33 base at the A site is a key event in the mechanism of codon recognition.

著者

内藤 結花 石井 正和 川名 慶治 坂入 由貴 清水 俊一 木内 祐二

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.129, no.6, pp.735-740, 2009-06-01 (Released:2009-06-01)

参考文献数

9

被引用文献数

5 8

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Pharmacists in a community pharmacy may recommend an over-the-counter (OTC) drug to patients with headache. However, it is not clear how pharmacists should distinguish the symptoms of patients and facilitate appropriate self-medication. Here, we investigated the role of pharmacists in a community pharmacy in recommending OTC drugs for self-medication by patients with headache and elucidated their future needs using a questionnaire intended for doctors and pharmacists. More than half of the pharmacists surveyed did not have any experience with recommending OTC drugs for patients with headache. To distinguish between patients for whom pharmacists should “recommend OTC drugs” and patients who should be encouraged “to consult a hospital or clinic,” doctors thought that pharmacists should use an “assistance tool to diagnosis headache, such as a screener for migraine” and “guidelines for chronic headache.” However, few pharmacists used these tools. About 68% of doctors indicated that it would be “meaningful” for pharmacists to distinguish patients with headache. Moreover, both doctors and pharmacists thought that pharmacists should provide patients not only with “instruction on the use of drugs” but also suggest “when to consult a hospital or clinic.” However, 32% of doctors indicated that it is “meaningless” for pharmacists to attempt to distinguish patients with headache and expressed concern about the increase of patients who overuse headache medication. These findings provide useful information to guide pharmacists in community pharmacy when recommending OTC drugs for self-medication by patients with headache.

著者

古武 弥一郎

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.138, no.10, pp.1227-1233, 2018-10-01 (Released:2018-10-01)

参考文献数

37

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It is pivotal to assess the toxicity and safety of chemicals, including medicines, in the research field of environmental health science. Here we introduce neurotoxic mechanisms in mammals of environmental organotin and Parkinson's disease-related chemicals. We clarified that low concentrations of tributyltin decrease α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)-type glutamate receptor subunit GluA2 (GluR2) expression, leading to the vulnerability of cultured neurons. That is, tributyltin reduces GluA2 prior to neuronal death. This GluA2 decrease can be used as a sensitive evaluation index of neurotoxicity, since low levels of certain chemicals, for example some agrochemicals, decrease GluA2 expression. We also elucidated the mechanisms of abnormal protein metabolism induced by low levels of two Parkinson's disease-related chemicals: 1-methyl-4-phenylpyridinium ion (MPP+) and 1,2,3,4-tetrahydroisoquinoline derivatives. It is expected that these findings will become clues in accurately evaluating the toxicity of chemicals and/or in investigating the causes of disease.

著者

福田 春香 鈴木 豊史 橋崎 要 吉村 彩也香 小林 千翔 重谷 美子 鈴木 直人 金沢 貴憲 深水 啓朗 山本 佳久

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.2, pp.299-308, 2019-02-01 (Released:2019-02-01)

参考文献数

21

被引用文献数

2

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To clarify the volume of water required to paste pediatric powders, we herein established a standard for the powder paste state by measuring yield values when water was added to powders. The powders used in the present study were selected from 8 types including original and generic drugs. Tipepidine hibenzate is prescribed in the pediatric field in combination with ambroxol hydrochloride and l-carbocysteine. The volumes of water needed to achieve the paste state of ambroxol hydrochloride between the original and generic drugs were similar. However, the volumes of water needed for l-carbocysteine markedly differed between the original and generic drugs due to differences in their additives. The spreadability of the mixture when water was added to the powders was evaluated using a spread meter. Among the powders tested in the present study, the yield value to achieve a paste state with the addition of water was approximately 1000 dyne/cm2. The optimum volume of water estimated from this yield value using the linear proportional relationship for the amount of powder may be applied to the mixture of each pediatric power for dosage/body weight.

著者

小田 紗矢香 冨田 拓郎 西田 基宏

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.138, no.10, pp.1257-1262, 2018-10-01 (Released:2018-10-01)

参考文献数

21

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Moderate exercise has been reported to combat several diseases, including cardiovascular diseases and depressants. However, many patients do not have ability to undergo exercise therapy due to aging and severity of the symptoms. Therefore development of new drugs that can imitate exercise therapy is desired and actually studied worldwide. The heart is one of the physical load-responsive target organs such as skeletal muscles and vascular smooth muscles. The heart can adapt from environmental stress by changing its structure and morphology (i.e., remodeling). Physiological remodeling, caused by exercise or pregnancy, can be defined by compensative and reversible changes to the heart, whereas pathological remodeling can be defined by irreversible changes of the heart, through aberrant calcium ion (Ca2+) signaling as well as production of reactive oxygen species (ROS). However, crosstalk between Ca2+ and ROS remains obscure. In this review we will introduce our recent findings on the functional crosstalk between transient receptor potential canonical (TRPC) 3 and nicotinamide adenine dinucleotide phosphate (NADPH) oxidase (Nox) 2 as a novel molecular target to mimic exercise therapy.

著者

水谷 秀樹

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.127, no.11, pp.1837-1842, 2007-11-01 (Released:2007-11-01)

参考文献数

19

被引用文献数

17 32

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A number of anticancer drugs exert their effect by causing DNA damage and subsequent apoptosis induction. Reactive oxygen species (ROS), such as hydrogen peroxide (H2O2) and super oxide anion (O2-), participate in apoptosis and DNA damage induced by some anticancer drugs, however, the precise mechanism of apoptosis via ROS formation remains to be clarified. I investigated the mechanism of apoptosis and DNA damage induced by anticancer drugs, especially topoisomerase inhibitors, using human cultured cells. TAS-103, a topoisomerase inhibitor, induces apoptosis through DNA cleavage and subsequent H2O2 generation mediated by poly (ADP-ribose) polymerase (PARP) and NAD(P)H oxidase activation. Doxorubicin (DOX), an anthracycline antibiotic and topoisomerase inhibitor, induces apoptosis through direct oxidative DNA damage leading to indirect H2O2 generation mediated by PARP and NAD(P)H oxidase activation. DOX caused site-specific oxidative DNA damage in the presence of copper(II), which may contribute to apoptosis. These findings suggest that ROS formation plays important roles in apoptosis induced by anticancer drugs. Furthermore, these studies may provide an insight into the development of new effective chemotherapeutic drugs.

著者

鈴木 一衛 宮嵜 靖則 内野 智信 賀川 義之

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

vol.131, no.11, pp.1645-1651, 2011 (Released:2011-11-01)

参考文献数

11

被引用文献数

1 2

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Marketing authorization holders do not disclose any information on the pharmaceutical properties of over-the-counter drugs (OTC). When a drug is switched from a prescription drug to OTC, pharmacists can acquire that information from the corresponding ethical drug (ED) through the package insert, interview form, and so on. However, the pharmaceutical equivalence between ED and OTC is unclear. In this study, we examined the drug dissolution behavior of both ED and OTCs containing scopolamine butylbromide. Dissolution tests were performed by the paddle method using Japanese Pharmacopeia (JP) XV test fluids at pH 1.2, 4.0 and 6.8 and water based on the guidelines for bioequivalence studies of generic products. The dissolution profiles of OTCs differed significantly from ED showing a similarity factor (f2) value ranging from 8.9 to 42.9. Time until 85% dissolution ranged from 23 to 95 min and from 17 to 174 min at pH 1.2 and pH 6.8, respectively. Then JP XV disintegration tests were conducted to investigate differences in the disintegration process. The disintegration time of preparations showing delayed dissolution was prolonged compared to that of others, suggesting that the disintegration of the tablet or capsule is one of the important factors affecting the drug dissolution. These differences in the disintegration and drug dissolution might cause differences in the bioavailability of the drug. For patient safety, more detailed product information of OTCs should be supplied by the manufacturer, and not be assumed from that of corresponding ED.

著者

田口 恭治

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.2, pp.287-296, 2016-02-01 (Released:2016-02-01)

参考文献数

72

被引用文献数

8

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Peripheral neuropathy is a common adverse effect of paclitaxel and oxaliplatin treatment. The major dose-limiting side effect of these drugs is peripheral sensory neuropathy. The symptoms of paclitaxel-induced neuropathy are mostly sensory and peripheral in nature, consisting of mechanical allodynia/hyperalgesia, tingling, and numbness. Oxaliplatin-induced neurotoxicity manifests as rapid-onset neuropathic symptoms that are exacerbated by cold exposure and as chronic neuropathy that develops after several treatment cycles. Although many basic and clinical researchers have studied anticancer drug-induced peripheral neuropathy, the mechanism is not well understood. In this review, we focus on (1) analysis of transient receptor potential vanilloid 1 (TRPV1) channel expression in the rat dorsal root ganglion (DRG) after paclitaxel treatment and (2) analysis of transient receptor potential ankyrin 1 (TRPA1) channel in the DRG after oxaliplatin treatment. This review describes that (1) paclitaxel-induced neuropathic pain may be the result of up-regulation of TRPV1 in small- and medium-diameter DRG neurons. In addition, paclitaxel treatment increases the release of substance P, but not calcitonin gene-related peptide, in the superficial layers of the spinal dorsal horn. (2) TRPA1 expression via activation of p38 mitogen-activated protein kinase in small-diameter DRG neurons, at least in part, contributes to the development of oxaliplatin-induced acute cold hyperalgesia. We suggest that TRPV1 or TRPA1 antagonists may be potential therapeutic lead compounds for treating anticancer drug-induced peripheral neuropathy.

著者

本間 真人 石原 三也 千 文 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.126, no.10, pp.973-978, 2006 (Released:2006-10-01)

参考文献数

33

被引用文献数

19 32

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Typical adverse effects of Shakuyaku-kanzo-To (SKT), an herbal medicine containing licorice, is a licorice-induced pseudoaldosteronism with hypokalemia and hypertension. The risk factors for this side effect are still unclear. To identify the risk factors, we surveyed 37 cases of licorice-induced pseudoaldosteronism in the literature and serum potassium levels in our patients receiving SKT and Shosaiko-To (SST), which contain 6 g and 1.5 g of licorice in the daily dose, respectively. In the case report survey, pseudoaldosteronism developed a median 35 (range 2—231) days after the administration of SKT, which is shorter than after SST (450, range 150—2190 days) and other licorice products including glycyrrhizin (210, range 14—730 days). A significant correlation was observed between the glycyrrhizin contents in the licorice preparations and the dosing periods for developing pseudoaldosteronism (r=-0.700, p < 0.01). A negative correlation was also observed between serum potassium level and dosing period for SKT, but not for SST. The difference in age (65.3 ± 11.6 vs. 57.2 ± 17.3 y) and dosing period (57.3 ± 66.3 vs. 19.0 ± 24.3 days) between the patients with and without hypokalemia after the administration of SKT was statistically significant (p < 0.05). The occurrence rate of hypokalemia including pseudoaldosteronism was around 80% with SKT administration for more than 30 days for patients exceeding 60 years old. It was suggested that patient age (>60 y) and dosing period of SKT (>30 days) might be risk factors for developing pseudoaldosteronism or hypokalemia as well as coadministration of drugs inducing hypokalemia.

著者

山本 友子

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.126, no.12, pp.1235-1243, 2006 (Released:2006-12-01)

参考文献数

46

被引用文献数

4 4

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Phagocytosis with macrophages provides a specialized mechanism for regulated ingestion and intracellular destruction of bacteria. Bacteria are first engulfed by endocytosis into a phagosome. The fusion of phagosomes and lysosomes releases toxic products that kill most bacteria and degrade them into fragments. Debris from dead bacteria is then released by exocytosis. However, some bacteria that survive within host phagocytes have evolved strategies to escape the bactericidal mechanisms associated with phagocytosis: i) antiphagocytosis (Yersinia), ii) escaping from the phagosome into cytoplasm (Listeria), and iii) remodeling their phagosome by inhibiting the maturation of phagosomes (Salmonella, Mycobacterium, Legionella). In this review, I first summarize various strategies by bacteria to avoid phagocytosis by emphasizing the steps that have been subverted by bacteria. Then, I highlight the mechanisms for surviving phagocytosis by Salmonella, with a focus on the induction of macrophage-apoptosis and modulation of membrane traffic in host cells.

著者

荒井 研祐 三堀 将寛

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.138, no.4, pp.525-527, 2018 (Released:2018-04-01)

参考文献数

2

被引用文献数

1

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Within school classrooms, Active Learning has been receiving unprecedented attention. Indeed, Active Learning's popularity does not stop in the classroom. As more and more people argue that the Japanese government needs to renew guidelines for education, Active Learning has surfaced as a method capable of providing the necessary knowledge and training for people in all areas of society, helping them reach their full potential. It has become accepted that Active Learning is more effective over the passive listening of lectures, where there is little to no interaction. Active Learning emphasizes that learners explain their thoughts, ask questions, and express their opinions, resulting in a better retention rate of the subject at hand. In this review, I introduce an Active Learning support tool developed at Digital Knowledge, “Clica”. This tool is currently being used at many educational institutions. I will also introduce an online questionnaire that Digital Knowledge provided at the 10th Annual Meeting of the Japanese Society for Pharmaceutical Palliative Care and Sciences.

著者

杉原 数美

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.138, no.3, pp.277-280, 2018 (Released:2018-03-01)

参考文献数

10

被引用文献数

6

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In recent years, pharmaceuticals and personal care products (PPCPs) have emerged as significant pollutants of aquatic environments and have been detected at levels in the range of ng/L to μg/L. The source of PPCPs is humans and livestock that have been administered pharmaceuticals and subsequently excreted them via urine and feces. Unlike agricultural chemicals, the environmental dynamics of PPCPs is not examined and they would undergo structural transformation by environmental factors, e.g., sunlight, microorganisms and treatments in sewage treatment plants (STPs). Processing at STPs can remove various PPCPs; however, they are not removed completely and some persist in the effluents. In this study, we examined the degradation of 9 pharmaceuticals (acetaminophen, amiodarone, dapsone, dexamethasone, indomethacin, raloxifene, phenytoin, naproxen, and sulindac) by sunlight or UV, and investigated the ecotoxicological variation of degradation products. Sunlight (UVA and UVB) degraded most pharmaceuticals, except acetaminophen and phenytoin. Similar results were obtained with UVB and UVA. All the pharmaceuticals were photodegraded by UVC, which is used for sterilization in STPs. Ecotoxicity assay using the luminescent bacteria test (ISO11348) indicated that UVC irradiation increased the toxicity of acetaminophen and phenytoin significantly. The photodegraded product of acetaminophen was identified as 1-(2-amino-5-hydroxyphenyl)ethanone and that of phenytoin as benzophenone, and the authentic compounds showed high toxicity. Photodegraded products of PPCPs are a concern in ecotoxicology.

著者

朝比奈 泰彦 淺野 三千三

出版者

公益社団法人日本薬学会

雑誌

藥學雜誌 (ISSN:00316903)

巻号頁・発行日

no.480, pp.85-97, 1922-02-26

著者

加藤 隆弘 兵藤 文紀 大和 真由実 内海 英雄 神庭 重信

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.135, no.5, pp.739-743, 2015 (Released:2015-05-01)

参考文献数

36

被引用文献数

2 5

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Altered antioxidant status has been implicated in schizophrenia. Microglia are major sources of free radicals such as superoxide in the brain, and play crucial roles in various brain diseases. Recent postmortem and imaging studies have indicated microglial activation in the brain of schizophrenia patients. Animal models that express some phenotypes of schizophrenia have revealed the underlying microglial pathology. In addition, minocycline, an antibiotic and the best known inhibitor of microglial activation, has therapeutic efficacy in schizophrenia. We have recently revealed that various antipsychotics directly affect microglia via proinflammatory reactions such as oxidative stress, by in vitro studies using rodent microglial cells. Based on these findings, we have suggested that microglia are crucial players in the brain in schizophrenia, and modulating microglia may be a novel therapeutic target. In this review paper, we introduce our hypothesis based on the above evidence. The technique of in vivo molecular redox imaging is expected to be a powerful tool to clarify this hypothesis.

著者

笹岡 沙也加 畠平 春奈 長谷川 栞 元岡 佑美 福田 昌穂 長沼 美紗 梅津 亮冴 中尾 智史 島内 あかり 上田 夏実 平出 耕石 井口 和弘 中村 光浩

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.138, no.1, pp.123-134, 2018 (Released:2018-01-01)

参考文献数

22

被引用文献数

8

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OTC combination cold remedies are widely used in Japan. In the present study, we aimed to evaluate the adverse event profiles of OTC combination cold remedy based on the components using the Japanese Adverse Drug Event Report (JADER) database. The JADER database contained 430587 reports between April 2004 and November 2016. 1084 adverse events associated with the use of OTC combination cold remedy were reported. Reporting odds ratio (ROR) was used to detect safety signals. The ROR values for “skin and subcutaneous tissue disorders”, “hepatobiliary disorders”, and “immune system disorders” stratified by system organ class of the Medical Dictionary for Regulatory Activities (MedDRA) were 9.82 (8.71-11.06), 2.63 (2.25-3.07), and 3.13 (2.63-3.74), respectively. OTC combination cold remedy containing acetaminophen exhibited a significantly higher reporting ratio for “hepatobiliary disorders” than OTC combination cold remedy without acetaminophen. We demonstrated the potential risk of OTC combination cold remedy in a real-life setting. Our results suggested that the monitoring of individuals using OTC combination cold remedy is important.

著者

見坂 武彦 片岡 憲司 藤光 隆司 谷 佳津治

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.138, no.1, pp.117-122, 2018 (Released:2018-01-01)

参考文献数

21

被引用文献数

5

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Migratory birds are considered as vectors of infectious diseases, owing to their potential for transmitting pathogens over large distances. The populations of barn swallow (Hirundo rustica) migrate from Southeast Asia to the Japanese mainland during spring and migrate back to Southeast Asia during autumn. This migratory population is estimated to comprise approximately hundreds to thousands of individuals per year. However, to date, not much is known about the gastrointestinal microbiota of the barn swallow. In this study, we characterized the fecal bacterial community in barn swallow. Using 16S rRNA gene metagenomic sequencing analysis, we examined the presence and composition of potentially pathogenic bacteria in the fecal samples, which were collected during spring season from Osaka. The number (±S.D.) of total bacteria was approximately 2.1(±3.4)×108 per gram of feces. In most samples, the bacterial community composition was dominated by families, such as Enterobacteriaceae, Pseudomonadaceae, Mycoplasmataceae, Enterococcaceae, Streptococcaceae, and Alcaligenaceae. However, no relationship was found between the bacterial community composition and geographical area in the fecal samples. Potentially pathogenic bacteria were detected at the rate of >0.1%, which included Pseudomonas spp., Escherichia/Shigella spp., Enterobacter spp., Yersinia spp., Mycoplasma spp., Enterococcus spp., Achromobacter spp., and Serratia spp. Our results suggested that barn swallow is instrumental in the transmission of these genera over large distances.

著者

武富 芳隆 村上 誠

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.1, pp.73-84, 2011 (Released:2011-01-01)

参考文献数

71

被引用文献数

2 3

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Tissue-resident mast cells are derived from circulating committed progenitors, which are originated from pluripotential hematopoietic stem cells in bone marrow. These progenitors migrate into extravascular tissues, where they undergo differentiation and maturation into tissue-specific mature phenotypes. When activated by IgE/antigen, stem cell factor, neuropeptides, or other stimuli, mature mast cells release three classes of biologically active products, including pre-formed mediators stored in secretory granules, newly transcribed cytokines and chemokines, and de novo synthesized lipid mediators. Therefore, these cells have been implicated as major effector cells in acute and chronic inflammatory diseases. In recent years, it has become clear that lipid mediators including arachidonic acid metabolites (prostaglandins and leukotrienes) and lysophospholipid-derived products play crucial roles in mast cell-associated pathology. In this article, we will provide an overview of the roles of various lipid mediators in allergic diseases fueled by studies of their biosynthetic enzymes or receptors. In the latter part, we will make a particular focus on phospholipase A2 enzymes, which are placed at the bottleneck (rate-limiting) step of the lipid mediator-biosynthetic pathways.

著者

堀 誠治

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.10, pp.1423-1428, 2011 (Released:2011-10-01)

参考文献数

13

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Many antibiotics have been developed and used for the treatment of infectious diseases. Although they have been known to have various adverse effects, most of the mechanisms remain still unknown. New quinolones are well known to induce convulsions and their convulsant activity enhanced by concurrent administration of anti-inflammatory drugs. Each new quinolone has an individual convulsant activity with individual drug-interaction with anti-inflammatory drugs. And enoxacin, lomefloxacin and gatifloxacin have been reported to decrease blood glucose levels in a dose-depend- ent manner, but ciprofloxacin and levofloxacin had no effect on the levels. It should be important to know the safety profile of antimicrobial agents before doctors administer these agents to the patients with infectious diseases.

著者

舩田 正彦

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.136, no.1, pp.65-72, 2016 (Released:2016-01-01)

参考文献数

17

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Cases of people experiencing disturbed consciousness or dyspnea, causing traffic accidents, or requiring ambulance transport to hospital due to abuse of law-evading chemical substances have become a serious social problem in Japan. Most law-evading herbal products are marketed as incense or herbs and consist of finely chopped, dry vegetative matter mixed with chemical substances (drugs). Analysis of the chemical substances in these herbal products has demonstrated that they contain synthetic cannabinoids. Because there are many cannabinoid compounds, even if a particular drug is regulated, similar compounds that differ only slightly in structure may be added in their place. Therefore a cat-and-mouse game exists between regulations on chemical substances and their propagation. This paper summarizes the pharmacological actions and dangers of chemical substances contained in law-evading herbal products by focusing on synthetic cannabinoids, as a group of chemical substances contained in these products. Furthermore, comprehensive designations of synthetic cannabinoids have been introduced as a new method of regulation that emphasizes the similarity of chemical structures; this paper also outlines the comprehensive designations. We established a psychic-dependence liability and cytotoxicity screening system for synthetic cannabinoids using animals (behavioral analysis in vivo) and cell cultures (cytotoxicity analysis in vitro). With our drug-screening system, we were able rapidly to evaluate and quantify psychic-dependence liabilities and cytotoxicity of synthetic cannabinoids contained in law-evading herbal products. These scientific data using our screening system contributed to the establishment of legislation for comprehensive designations of synthetic cannabinoids.

著者

石井 敬 戸田 雄大 五十嵐 信智 落合 和 杉山 清

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.301-310, 2012 (Released:2012-03-01)

参考文献数

36

被引用文献数

2 14

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Living organisms eliminate foreign low-antigenic substances, such as drugs and environmental pollutants, by detoxification mediated by metabolizing cytochrome P450 (CYP). We have examined the possible regulation of CYP expression by enteric bacteria. Cyp mRNA expression levels, Cyp3a protein expression level, and the activity of Cyp3a in hepatic microsomal fractions were compared in germ-free (GF) and specific pathogen-free (SPF) mice. We evaluated hepatic Cyp3a11 mRNA expression levels and Cyp3a metabolic activity in GF and SPF mice after five days of antibiotic administration. The fecal levels of lithocholic acid (LCA)-producing bacteria and hepatic taurolithocholic acid (TLCA) were also measured. Cyp mRNA expression levels, Cyp3a protein expression level, and the activity of Cyp3a in SPF mice were higher than those in GF mice, indicating that enteric bacteria increases hepatic Cyp3a expression. The effects of enteric bacteria-reducing antibiotics on Cyp3a expression were examined. We observed that decreasing enteric bacteria with antibiotics in SPF mice caused a significant decrease in the hepatic Cyp3a11 mRNA expression, TLCA, and fecal LCA-producing bacteria compared to the group that did not receive antibiotics. No change in Cyp3a11 expression was observed in GF mice that were treated with antibiotics. Administration of LCA to GF mice showed an increase in Cyp3a11 expression similar to that of SPF mice. The enzymes of the enteric bacteria are believed to metabolize and detoxify drugs by either reduction or hydrolysis. The results of this study indicate that changes in enteric bacteria may alter the expression and activity of hepatic drug metabolizing enzymes and pharmacokinetics. Therefore, enteric bacteria should be closely monitored to ensure the safe use of drugs.