著者

松浦 巌 清家 康子 川真田 正信

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.103, no.1, pp.85-93, 1983-01-25 (Released:2008-05-30)

参考文献数

14

被引用文献数

1 1

---

Kinetic analysis of thermal decomposition was carried out using thermogravimetry (TG) and differential scanning calorimetry (DSC). The linear equations of n order, phase-boundary, nucleation growth and diffusion-controlled reaction under linear heating conditions were derived for the estimation of the rate constant and the activation energy. The method to determine the reaction mechanism was shown by evaluation of linearity. The equations were applied to the TG and DSC curves of dehydration of calcium oxalate monohydrate and elimination of carbon monoxide from calcium oxalate. The dehydration was fit to two-dimensional phase-boundary reaction and the activation energy was calculated as 85 kJ/mol. But the dehydration at a high-speed heating rate proceeded as apparent three-dimensional diffusion-controlled reaction. The elimination of carbon monoxide from calcium oxalate was fit to phase-boundary reaction and the activation energy was calculated as 196 kJ/mol for three-dimensional phase-boundary reaction and 182 kJ/mol for two-dimensional phase-boundary reaction.

著者

山口 寿 川真田 正信 仲井 由宣 山本 恵司

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.102, no.5, pp.463-468, 1982-05-25 (Released:2008-05-30)

参考文献数

8

被引用文献数

1 1

---

By use of X-ray diffractometry, thermal analysis and infrared spectroscopy, the crystal forms of N-(2, 6-dimethylphenyl)-Δ8-dihydroabietamide were investigated. Two polymorphic forms (form I and II), two solvates (cyclohexane and CCl4), and an amorphous form were identified. Heating of form II induced a solid transformation to form I. The transition of form I and II to the amorphous form was observed by grinding. Each solvate contained 9.0% cyclohexane and 16.0% CCl4 respectively, i.e., drug : solvent=2 : 1. The activation energy of the desolvation was determined from TG curves by using Ozawa's method, and calculated as 72.2 kcal/mol for the cyclohexar solvente, and 35.5 kcal/mol for the CCl4 solvate.

著者

勝見 英正 草森 浩輔 坂根 稔康 山本 昌

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.9, pp.1129-1133, 2010 (Released:2010-09-01)

参考文献数

19

被引用文献数

7 6

---

Bisphosphonates are carbon-substituted pyrophosphate (PCP) analogues that exhibit high affinity to hydroxylapatite and inhibit bone resorption after their administration. They are widely used as the first-choice drug for the treatment and prevention of bone diseases, including Paget's disease, hypercalcemia of malignancy, and osteoporosis. However, the oral bioavailability of bisphosphonates is quite low (1-2%). In addition, the oral administration of bisphosphonates has been associated with mucosal damage, including gastritis, gastric ulcer, and erosive esophagitis. Therefore, it is highly desirable to develop new delivery systems that improve their bioavailability and safety. In this review, recent challenges in the developments of novel delivery system of bisphosphonates are summarized. Then, future developments of delivery system of bisphosphonates are also discussed in order to improve their therapeutic efficacy and safety in the treatment of bone diseases.

著者

畠山 大

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.2, pp.205-214, 2017 (Released:2017-02-01)

参考文献数

40

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The PA, PB1, and PB2 subunits, components of the RNA-dependent RNA polymerase of influenza A virus, and the nucleoprotein (NP) interact with the genomic RNA of influenza viruses and form ribonucleoproteins. Especially, the PB2 subunit binds to the host RNA cap [7-methylguanosine triphosphate (m7GTP)] and supports the endonuclease activity of PA to “snatch” the cap from host pre-mRNAs. In this study, we describe a novel Val/Arg/Gly (VRG) site in the PB2 cap-binding domain, which is necessary for interaction with acetyl-CoA found in eukaryotic histone acetyltransferases (HATs). In vitro experiments revealed that the recombinant PB2 cap-binding domain that includes the VRG site interacts with acetyl-CoA; moreover, it was found that this interaction could be blocked by CoA and various HAT inhibitors. Interestingly, m7GTP also inhibited this interaction, suggesting that the same active pocket is capable of interacting with acetyl-CoA and m7GTP. To elucidate the importance of the VRG site on PB2 function and viral replication, we constructed a PB2 recombinant protein and recombinant viruses including several patterns of amino acid mutations in the VRG site. Substitutions of 2 or 3 amino acid residues of the VRG site to alanine significantly reduced PB2's binding ability to acetyl-CoA and its RNA polymerase activity. Recombinant viruses containing the same mutations could not be replicated in cultured cells. These results indicate that the PB2 VRG sequence is a functional site that is essential for acetyl-CoA interaction, RNA polymerase activity, and viral replication. I will also discuss some novel functions of NP in this review.

著者

清水 万紀子

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.129, no.11, pp.1351-1356, 2009 (Released:2009-11-01)

参考文献数

23

被引用文献数

1 2

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Individual differences of drug-metabolizing enzymes are important determinants for the metabolic fate of chemicals. This article focuses on polymorphic human flavin-containing monooxygenase 3 (FMO3) and dietary-derived trimethylamine. Malodorous trimethylamine is generally converted to odorless trimethylamine N-oxide by liver microsomal FMO3. Trimethylaminuria is caused by functional disorder of FMO3. In this study mutations of the FMO3 gene were examined in self-reported Japanese trimethylaminuria subjects that showed low FMO3 metabolic capacity in urine tests. Nine novel polymorphisms in the FMO3 gene were discovered in self-reported Japanese volunteers. Functional analyses of recombinant FMO3 proteins suggested that these FMO3 gene mutations were one of the causal factors for decreased FMO3 function resulting in trimethylaminuria. Inter-individual variations of FMO3-mediated microsomal oxygenation activities, levels of FMO3 protein and FMO3 mRNA, and its modification in liver microsomes from Japanese samples were observed. Both genetic polymorphisms in the 5′-upstream of the FMO3 gene and some hormonal changes related to menstruation may be causal factors for inter- and/or intra- individual expression levels of FMO3. To assess the palliative cares, it was found that absorbed levels of trimethylamine in vivo would be possibly controlled by selection of precursor foods like fish containing a variety of trimethylamine amounts. These lines of evidence suggest that individual differences of FMO3 are important determinants for the metabolic fate of dietary-derived trimethylamine.

著者

木村 善行 大南 宏治 有地 英子 奥田 拓道 有地 滋 林 輝明

出版者

公益社団法人日本薬学会

雑誌

薬学雑誌 (ISSN:00316903)

巻号頁・発行日

vol.102, no.7, pp.p666-669, 1982-07

被引用文献数

2

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It was found that high sugar diets induced an elevation in serum levels of triglyceride and insulin in rats by the oral administration for 2 months. When black substances isolated from crude black sugar were orally administered to rats with the high sugar diets, such elevation was not observed. In addition to these effects, black substances were found to reduce serum lipid peroxide. Black substances were found to inhibit absorption of glucose in the rat small intenstine. Therefore, it was suggested that the effect of black substances on hyperlipemia in rats fed with the high sugar diets might be partly attributable to an inhibition of glucose absorption in the small intenstine.

著者

高橋 典子

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.122, no.8, pp.547-563, 2002-08-01 (Released:2003-02-18)

参考文献数

79

被引用文献数

4 4

---

Cell differentiation is essential for normal growth and homeostasis, and drug-induced differentiation of tumor cells into benign or normal cells is an important approach for anticancer chemotherapy. Studies of induction mechanisms for cell differentiation and discovery of differentiation-inducing factors are thus critical components of drug development. The Screening of differentiation-inducing factors, such as purified aldehyde reductase, a xenobiotic metabolite enzyme, that induces differentiation of human acute myeloid leukemia HL60 cells into monocyte/macrophage cells is described. Mechanisms of all-trans-retinoic acid (RA)-induced differentiation are also covered. RA is a potent inducer of HL60 cell differentiation and when used as a sole agent it can induce complete remission in patients with acute promyelocytic leukemia (APL). While one mechanism of the effect of RA involves RA nuclear receptors, retinoylation (a posttranslational modification of proteins by RA) may be a new nongenomic mechanism by which RA acts on cells. An early event in RA-induced differentiation may be retinoylation of RIIα (regulatory subunits of cAMP-dependent protein kinase), in which RIIα units are retinoylated and the retinoylated RIIα is then translocated to the nucleus. Drugs can also be combined with RA in RA-differentiation therapy. Cytodifferation therapy by RA in APL patients exhibits limitations due to the resistance of relapsed patients to further RA treatment. This may occur through the induction of expression of various genes that reduce RA blood concentrations. Treatment with combinations of RA and other agents may be one way to reduce induction of those genes. Good candidates for such agents include cAMP-elevating agents, retinoids, steroids, and fatty acids that synergistically induce differentiation of HL60 cells. Two derivatives of falconensone A, falconensone A p-bromophenylhydrazone, which has a bromophenyl residue, and falconensone A dioxime, which possesses a hydroxy residue, were synthesized to incorporate features of RA and N-[4-hydroxyphenyl]retinamide. Both derivatives have exhibited more potent biological activity than the parent falconensone A in vitro and in vivo.

著者

猪熊 翼 佐藤 伸一

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.138, no.1, pp.37-38, 2018 (Released:2018-01-01)

著者

落合 英二 小林 五郎 林 英作 野口 雄一郎

出版者

公益社団法人 日本薬学会

雑誌

薬学雑誌. 乙号 (ISSN:00316903)

巻号頁・発行日

vol.66, no.7-12, pp.78-81, 1953-10-25 (Released:2009-10-22)

参考文献数

5

著者

寺町 ひとみ 杉田 郁人 伊野 陽子 林 勇汰 吉田 阿希 大坪 愛実 上野 杏莉 勝野 隼人 野口 義紘 井口 和弘 舘 知也

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.9, pp.1177-1184, 2017 (Released:2017-09-01)

参考文献数

21

被引用文献数

4

---

We analyzed impression data and the scale of communication skills of students using text mining method to clarify which area a student was conscious of in communication in practical training. The results revealed that students tended to be conscious of the difference between practical hospital training and practical pharmacy training. In practical hospital training, specific expressions denoting relationships were “patient-visit”, “counseling-conduct”, “patient-counseling”, and “patient-talk”. In practical pharmacy training, specific expressions denoting relationships were “patient counseling-conduct”, “story-listen”, “patient-many”, and “patient-visit”. In practical hospital training, the word “patient” was connected to many words suggesting that students were conscious of a patient-centered communication. In practical pharmacy training, words such as “patient counseling”, “patient”, and “explanation” were placed in center and connected with many other words and there was an independent relationship between “communication” and “accept”. In conclusion, it was suggested that students attempted active patient-centered communication in practical hospital training, while they were conscious of listening closely in patient counseling in practical pharmacy training.

著者

山野 喜昭 池谷 理 大前 雅彦 河部 靖

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.99, no.11, pp.1102-1110, 1979-11-25 (Released:2008-05-30)

参考文献数

8

被引用文献数

2 8

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In order to study cis-trans photo-isomerization of phylloquinone (K) and menaquinone-4 (MK-4), a high-performance liquid chromatographic method for the determination of cis-trans isomers was developed. After removal of the surface active agent and photo-decomposition products, cis-trans isomers were separated on a Nucleosil 50 (particle size ; 5 μm) column using di-n-butyl ether-n-hexane (6 : 94) as a mobile phase. The internal standards used were MK-4 for K and K for MK-4. When either cis or trans compound of K and MK-4 were photo-irradiated in benzene, cis⇌trans photo-isomerization was observed and an equilibrium favoring the trans isomers was attained. Trans→cis photo-isomerization of MK-4 was also observed in injection and in infusion solution. Photo-isomerization and photolysis in their solution were inhibited considerably by using a light-intercepting shade.

著者

宮崎 正三 堀 了平 有田 隆一

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.95, no.6, pp.629-633, 1975-06-25 (Released:2008-05-30)

参考文献数

14

被引用文献数

2 6

---

Four different solid phases of tetracycline (trihydrate, anhydrate, dehydrate, and amorphous) were isolated. These phases were characterized by using IR spectroscopy, X-ray powder diffraction, and thermogravimetric and differential thermal analyses. Dissolution behavior of these phases in distilled water was investigated and an appreciable difference in the dissolution behavior was detected between the amorphous and the other solid phases. The effect of the solid phases on bioavailability of tetracycline was also studied. Blood plasma levels obtained in rabbits and blood levels in rats after intraduodenal administration of the trihydrate and amorphous were compared, and its results indicated that the solubility difference between the two phases has an effect on the bioavailability of tetracycline. The cumulative excretion of tetracyc1ine in urine after oral administration of the two phases to human subjects was also examined and its results indicated that the cumulative amount after administration of the amorphous was slightly higher than that of the trihydrate.

著者

湯浅 龍三 今井 淳 森川 裕司 草嶋 久生 内田 広 入倉 勉

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.102, no.5, pp.469-476, 1982-05-25 (Released:2008-05-30)

参考文献数

9

被引用文献数

2 6

---

The presence of three kinds of hydrates of AM-715 (1-ethyl-6-fluoro-1, 4-dihydro-4-oxo-7-(1-piperazinyl)-3-quinolinecarboxylic acid) was confirmed by elemental analysis, Karl-Fischer method, thermogravimetric analysis, differential scanning calorimetry, infrared spectroscopy, and X-ray diffractometry. Anhydrous AM-715 was not hygroscopic under less than 36% of relative humidity, but easily transformed to 5/2-hydrate over 62-78% of relative humidity and 5-hydrate above 94% of relative humidity, at 40°C. Anhydrous AM-715 was transformed to 5/2-hydrate with the first-order kinetics and 5/2-hydrate was dehydrated according to the first-order kinetics with an activation energy of dehydration of 22 kcal/mol. The 5/2-hydrate was converted to 5-hydrate much slowly than anhydrous AM-715. Dissolution rates were determined in water by using tape procedure, showing a slight difference between anhydrous AM-715 and its hydrates. In order to determine the effect of hydration on bioavailability, the serum levels in dogs were measured after oral administration. There were no significant differences among bioavailability of anhydrous AM-715, its 5/2-hydrate and 5-hydrate.

著者

國友 勝

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.12, pp.1997-2014, 2007 (Released:2007-12-01)

参考文献数

108

被引用文献数

16 26

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Oxidative stress is a continuous level of oxidative damage in animal cells, which is caused by an overabundance of reactive oxygen species or a decline in antioxidant ability against them. Oxidative stress increases with individual risk factors of atherosclerosis such as obesity, hypertension, hyperlipidemia, diabetes and smoking. Thus, oxidative stress is considered to play a key role in the pathogenesis of atherosclerosis. This review discusses the relationship between oxidative stress and atherosclerosis based on findings from our research group. We have found that atherosclerotic lesions are formed in the aorta of mice fed a high-cholesterol and high-linoleic diet, in parallel with elevated serum lipid peroxide levels. This model is useful for primary screening of antiatherosclerotic agents with antioxidative activity. One notable factor in the development of atherosclerosis is oxidized low-density lipoprotein (OxLDL). In order to examine OxLDL levels in blood, we have developed anion-exchange HPLC methods using stepwise elution. Using these methods, we have found that OxLDL markedly increases in a rat model of metabolic syndrome, in animals exposed to cigarette smoke and in smokers in parallel with other oxidative stress markers. These oxidative stress markers have been attenuated by administration of several antioxidants. In addition, we have found that smoking accelerates atherogenesis in the aorta of apoE-deficient mice and this acceleration can be ameliorated by administration of vitamin E. These observations suggest that antioxidant supplementation may be an effective therapeutic strategy for metabolic syndrome and smoking-induced diseases in which elevated oxidative stress plays a pivotal role.

著者

粟田 則男 山本 恵一 中川 寛 杉本 功 坂田 英彦 佐藤 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.99, no.2, pp.141-145, 1979-02-25 (Released:2008-05-30)

参考文献数

11

被引用文献数

1 2

---

Acebutolol hydrochloride was proved by thermal analysis (DTA and TG), IR spectra, and X-ray powder diffraction to have three crystalline forms (form I, II, and III) and an amorphous form. The amorphous form, which was stored at 20°under 91% R.H., was first transformed to forms II and III, and then it was finally transformed to form I. During this transformation, the incorporation and release of water were examined. Form I was stable at this condition, while form II was transformed to form I for 48 hr, and form III was transformed to form I for 2 hr. Further, it was found that the amorphous form was transformed to form II at 80°under 50% R.H. for 3 hr, but at 80°under vacuum it was transformed to form III. Form I at 138°for 8 hr and form III at 130°for 4 hr were transformed to form II. From these results it was concluded that form I was the most stable form at room temperature.

著者

岡田 芳男

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.10, pp.1141-1154, 2009 (Released:2009-10-01)

参考文献数

36

被引用文献数

3 5

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This review documents my research for the past 45 years in peptide chemistry. Initially, in order to study the structure-activity relationships of active center of α- and β-melanocyte stimulating hormones (H-His-Phe-Arg-Trp-Gly-OH), we employed D-amino acids. That approach yielded first published report in 1965 of antagonists containing D-amino acids. Monkey β-melanocyte stimulating hormone (β-MSH), an 18 amino acid peptide stimulated pigment cells. We synthesized β-MSH and fragments thereof, and studied in detail structure-activity relationships. A major and valuable result revealed that the C-terminal pentadecapeptide of β-MSH exhibited higher MSH activity than the parent hormone providing a new question; namely, what was the role of the N-terminal tripeptide? In order to identify the novel enzyme, spleen fibrinolytic proteinase (SFP), I developed a specific chromogenic substrate, Suc-Ala-Tyr-Leu-Val-pNA, and a specific inhibitor, Suc-Tyr-D-Leu-D-Val-pNA, once again employing my D-amino acid strategy. SFP was purified by affinity chromatography using Suc-Tyr-D-Leu-D-Val-pNA as the bound ligand. The success of this approach provided me the incentive to develop a variety of potential drugs. Thus, I prepared a specific plasmin inhibitor (YO-2) and a plasma kallikrein inhibitor (PKSI-527). Next, my research developed novel opioid receptor specific opioid agonists and antagonists based on 2′,6′-dimethyl-L-tyrosine (Dmt) dimers coupled with unique pyrazinone ring as a spacer. They exhibited potent oral antinociceptive activity acting through the μ-opioid receptor. Potent μ-receptor agonists (H-Dmt-Pro-Phe/Trp- Phe-NH2) were transformed into highly selective μ-receptor antagonists (N-allyl-Dmt-Pro-Phe/Trp-Phe-NH2), which reversed ethanol-induced increases in GABAergic neurotransmission, suggesting the possibility that they may emerge as candidates for the treatment of ethanol addiction.

著者

大谷 靖 川瀬 勝凡 林 敬一郎 龝本 晃 平山 宏 中村 勝一 小倉 勲

出版者

公益社団法人日本薬学会

雑誌

薬学雑誌 (ISSN:00316903)

巻号頁・発行日

vol.89, no.8, pp.1115-1118, 1969-08

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Formation of azulene from hydronaphthalene by the application of Lang's method was observed when using decalin as the starting material, with single metal such as iron and Raney nickel or activated carbon as a catalyst, and the amount of the product was greater when using trans-decalin rather than cis-decalin. This is considered to be due to the difference in the distance between hydrogen atoms at 5- and 9-positions. A part of the cis isomer was found to change into the trans type when heated. There was no formation of azulene when using tetralin as the starting material. The spectra of azulene solution after irradiation of ultraviolet or γ-rays showed smaller change in absorption intensity than that of guaiazulene. Irradiation of γ-rays on azulene solution was found to produce reduction and polymerization, as in the case of guaiazulene, from the result of gas chromatographic analysis. In the case of oxygen-containing compounds, irradiation with ultraviolet or γ-rays was found to produce turbidity but isolation and identification of this product were not possible due to the minute amount formed. These irradiation experiments indicated that azulenes without a side chain were more stable than guaiazulenes.

著者

国嶋 崇隆

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.128, no.3, pp.425-438, 2008 (Released:2008-03-01)

参考文献数

40

被引用文献数

1 3

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Reaction rates and selectivities can be critically affected by the reaction field. Using a diverse set of reagents and reaction systems, the author reviews a variety of ways to control the reaction field. In the first example, we discuss 4-(4,6-dimethoxy-1,3,5-triazin-2-yl)-4-methylmorpholinium chloride (DMT-MM), which serves as an exceptionally convenient reagent for dehydrocondensation. In particular, formation of carboxamide by DMT-MM was found to take place even if water or alcohol were used as a reaction medium. Thus, chemical modification of carboxyl groups and/or amino groups of highly polar substrates, such as amino acid derivatives, peptides, glyco-chains, and nucleotides, can be simply effected by mixing them with DMT-MM in aqueous or alcoholic solvents. The author also found that a tertiary amine catalyzes the activation step of carboxylic acid with 2-chloro-4,6-dimethoxy-1,3,5-triazine (CDMT) via in situ generation of coupling reagents. Proceeding further in this direction, we determined that artificial acyltransferase and cyclotransferase could be formed by conjugation of a tertiary amine catalyst to host-molecules to mimic a substrate binding site. Finally, the micellar interface, well known for promoting hydrolysis, clearly provides a superior reaction field for dehydrocondensation. When a 1,3,5-triazine-type amphiphilic dehydrocondensing agent was used, bimolecular dehydrocondensation between amphiphilic carboxylate and amines was highly accelerated (2000-fold) in a micellar system. Spontaneous membrane fusion was induced by adoption of the micellar reaction in the ceramide synthesis at the surface of membranes. All together, these diverse findings strongly support the central importance of the reaction field in controlling reaction rates and selectivity.

著者

芳生 秀光

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.9, pp.1143-1156, 2010 (Released:2010-09-01)

参考文献数

77

被引用文献数

2 5

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Mercury and its organic compounds, especially methylmercury are extremely hazardous pollutants that have been released into the environment in substantial quantities by natural events and anthropogenic activities. Due to the acute toxicity of these contaminants, there is an urgent need to develop an effective and affordable technology to remove them from the environments. Recently, attempts have been made to utilize bacterial mer operon-mediated reduction and volatilization of mercurials for environmental remediation of mercury pollution. However, application of this technology to the treatment of mercury-contaminated environments has been limited by social concerns about the release of volatile mercury that will become part of the local mercury cycle and repollute the environment again, into the ambient air. To improve this environmental problem, a new mercury scavenging mechanism that could be expressed in living cells and accumulates mercury from contaminated site without releasing mercury vapor is necessitated. To construct a new biocatalyst that is capable of specifically accumulating mercury from contaminated sites without releasing mercury vapor, we have genetically engineered bacteria and tobacco plant for removal of mercury from wastewater and soils, respectively, to express a mercury transport system and organomercurial lyase enzyme simultaneously, and overexpress polyphosphate, a chelator of divalent metals. The applicability of these new engineered biocatalysts in the environmental remediation of mercurials is evaluated and discussed in this review.

著者

冨田 隆志

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.12, pp.1497-1504, 2017 (Released:2017-12-01)

参考文献数

31

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Several issues concerning medicines remain unclear, including the availability of known, but not easily recognizable information. This review evaluates the mechanisms of side effects and the various risk indications included in package inserts. The results can be summarized as follows. 1) Short-term exposure to gatifloxacin significantly induced insulin secretion and increased the cytosolic Ca2+ concentration of islet cells by augmenting extracellular Ca2+ influx and its release from the endoplasmic reticulum. Alternatively, there was a decline in the cellular insulin level and reactivity to sulfonylurea after prolonged exposure. The insulin depletion was greater than that produced by other fluoroquinolones. 2) The elution of di(2-ethylhexyl)phthalate (DEHP) from the infusion set could be associated with the solubilizers in the injection medicines. The package inserts of several products containing polysorbate or ethanol had no warning about DEHP. Although there was a slight correlation between polysorbate content and descriptions on package inserts, the use of DEHP-containing devices was prohibited for some products, even with limited amounts of polysorbate. Therefore, the package insert statements should be reviewed to reflect appropriately the extent of DEHP elution. 3) Risk management plan consists of strategies to minimize the potential risks of medicines. One approach could be to introduce reminders on package inserts; however, of 268 potential risks associated with 81 products, 56 were not mentioned in package inserts. Because most postmarketing pharmacovigilance plans depend on spontaneous reporting by healthcare personnel, the descriptions on package inserts should be reexamined.