著者

鈴木 亮平 大津 史子 後藤 伸之

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.135, no.7, pp.895-916, 2015 (Released:2015-07-01)

参考文献数

10

被引用文献数

1

---

The purpose of this study was to develop and validate estimate equations for preventing adverse drug reactions (ADRs). We conducted five case-control studies to identify individual risk factors and subjective symptoms associated with the following five ADRs: drug-induced ischemic heart disease; renal damage; muscle disorder; interstitial pneumonia; and leucopenia. We performed logistic regression analysis and obtained eight regression equations for each ADR. We converted these to ADR estimate equations for predicting the likelihood of ADRs. We randomly selected 50 cases with non-individual ADRs from the Case Reports of Adverse Drug Reactions and Poisoning Information System (CARPIS) database of over 65000 case reports of ADRs, and assigned these cases to a validation case group. We then calculated the predictive probability for 50 cases using the eight estimate equations for each ADR. The highest probability for each ADR was set as the probability of each ADR. If the probability was over 50%, the case was interpreted as ADR-positive. We calculated and evaluated the sensitivity, specificity, and positive likelihood ratio of this system. Sensitivity of the estimate equations for muscle disorder and interstitial pneumonia were ≥90%. Specificity and positive likelihood ratios of estimate equations for renal damage, interstitial pneumonia and leucopenia were ≥80% and ≥5, respectively. Our estimate equations thus showed high validity, and are therefore helpful for the prevention or early detection of ADRs.

著者

廣瀬 順造

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.11, pp.1109-1124, 2014 (Released:2014-11-01)

参考文献数

42

被引用文献数

1

---

The metal dissociation constants of bovine carbonic anhydrase II, bovine carboxypeptidase A, rat aminopeptidase B, and rat dipeptidyl peptidase III were measured using metal buffer solutions. The zinc dissociation constants of bovine carbonic anhydrase II, bovine carboxypeptidase A, rat aminopeptidase B, and rat dipeptidyl peptidase III were 5.8×10−14, 3.5×10−12, 3.7×10−13, and 1.9×10−13 M, respectively. The ternary complex between metal derivatives of bovine carbonic anhydrase and various chelating agents were characterized using the kinetic method and visible and magnetic circular dichroism spectra. The coordination geometry of the ternary complex was in the equilibrium state between the five and the tetrahedral coordination geometry. The equilibrium state depends on the character of ligands. Dipeptidyl peptidase III which has an abnormal zinc binding motif (HEXXXH) was characterized using the point mutation and computer simulation methods. The abnormal zinc binding motif (HEXXXH) of rat dipeptidyl peptidase III has a large helix part. It is generally known that the cupric derivatives of the zinc peptidase loses enzyme activity, but the cupric derivative of dipeptidyl peptidase III surprisingly has enzyme activity. The measurement of the electron paramagnetic resonance spectra of the cupric rat dipeptidyl peptidase III in the presence of the substrate showed that the coordination geometry is very flexible. The flexibility of the coordination geometry in the cupric rat dipeptidyl peptidase III is important for the expression of enzyme activity. Docking simulation was used to identify the substrate binding site of aminopeptidase B, which is a powerful tool to estimate substrate binding residues in enzymes.

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.72, no.12, pp.e2ac-e2ac, 1952 (Released:2010-02-19)

著者

高橋 恭兵 立浪 良介 丹保 好子

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.128, no.10, pp.1443-1448, 2008 (Released:2008-10-01)

参考文献数

33

被引用文献数

7 11

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Diabetic patients exhibit increased blood plasma levels of methylglyoxal (MG), a metabolite of glucose. Since MG generates advanced glycation end-products (AGEs) that disrupt the functions of such biomolecules as proteins, it is responsible for the progression and complications of diabetes. A functional disorder of the vascular endothelium may also contribute to the progression and complications of diabetes. In endothelial cells, MG is the major precursor for the formation of AGEs. In this study, we examined the effects of MG on vascular endothelial cells and found that it induced the apoptosis of bovine aortic endothelial cells (BAECs). MG induced the collapse of mitochondrial membrane potential, an index of apoptosis, and the elevation of caspase-3 activity, an apoptotic execution enzyme, leading to cell death. Flow cytometric analyses with annexin-V and propidium iodide double staining revealed that cells exposed to a lethal dose of MG displayed features characteristic of apoptosis. MG induced an increase in the level of intracellular reactive oxygen species (ROS) prior to induction of apoptosis. Taken together, these findings suggest that BAECs exposed to MG die by apoptosis due to the increase of intracellular ROS level.

著者

水島 徹

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.6, pp.713-720, 2012 (Released:2012-06-01)

参考文献数

24

被引用文献数

2 4

---

As a new strategy for drug discovery and development, we propose here the establishment of drug re-profiling strategy. In this strategy, the actions of existing medicines, whose safety and pharmacokinetic effects in humans have been confirmed already, are examined comprehensively at the molecular level and the results are used for the development of new medicines. For example, identification of the mechanisms underlying the side effects of medicines enables us to develop safer drugs. The results can also be used for developing existing drugs for use as medicines in treatment of other diseases. Promoting this research strategy could provide breakthroughs in drug discovery and development by pharmaceutical companies.

著者

菅原 隆文 村上 礼隆 植竹 宣江 開 浩一

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.135, no.6, pp.829-833, 2015 (Released:2015-06-01)

参考文献数

10

被引用文献数

1

---

Recently, extended-spectrum β-lactamase (ESBL)-producing Escherichia coli has been more frequently isolated from blood specimens than in the past. In this study we investigated a panel of therapeutic agents used to treat 37 patients with ESBL-producing E. coli bacteremia. Antimicrobial agents administered as definitive therapy displayed higher efficacy rates than when empiric therapy was administered (efficacy rates, 95.7% vs. 62.5%). The success rate of carbapenem was 95.8% (23/24) in patients with ESBL-producing E. coli bacteremia. In addition, the success rate of cefmetazole against ESBL-producing E. coli sensitive to this drug was 87.5% (7/8). In conclusion, patients at high risk of infection due to ESBL-producing E. coli should be empirically treated with carbapenem antibiotics. In addition, cefmetazole may be a treatment option for patients with ESBL-producing E. coli bacteremia.

著者

溝口 優 桑野 紗子 鈴木 育子 重山 昌人

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.136, no.12, pp.1657-1666, 2016 (Released:2016-12-01)

参考文献数

13

被引用文献数

1

---

Although the removal of bacteria in the oral cavity is regarded as an important preventive measure against pneumonia, the majority of elderly individuals are rarely provided with oral care-related information. This study examined the usefulness of oral care-related information provision for the elderly by pharmacists working at drugstores. A questionnaire survey was conducted, involving 387 pharmacists working at drugstores and 51 elderly individuals who visited such stores. Oral care-related information had been actively provided by 14.5% of the pharmacists, and 62.5% of all oral care products were being sold as care products. When focusing on the elderly, 70.6% showed interest in oral care, but the proportion of those who had performed self-care to promote such health was limited to 5.9%. After being provided with oral care-information, 97.6% answered “I wish to regularly perform oral self-care”, and 86.3% regarded oral care-related information provision by pharmacists as “very useful”. The results of this study demonstrate the usefulness of information provision by pharmacists at drugstores to promote oral self-care among the elderly.

著者

竹田 修三

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.133, no.10, pp.1093-1101, 2013

被引用文献数

10

---

Considerable attention has focused on cannabidiol (CBD), a major non-psychotropic constituent of fiber-type <i>cannabis</i> plant, and it has been reported to possess diverse biological activities. Although CBD is obtained from non-enzymatic decarboxylation of its parent molecule, cannabidiolic acid (CBDA), several studies have investigated whether CBDA itself is biologically active. In the present report, the author summarizes findings indicating that; 1) CBDA is a selective cyclooxygenase-2 (COX-2) inhibitor, and ii) CBDA possesses an anti-migrative potential for highly invasive cancer cells, apparently through a mechanism involving inhibition of cAMP-dependent protein kinase A, coupled with an activation of the small GTPase, RhoA. Further, the author introduces recent findings on the medicinal chemistry and pharmacology of the CBD derivative, CBD-2′,6′-dimethyl ether (CBDD), that exhibits inhibitory activity toward 15-lipoxygenase (15-LOX), an enzyme responsible for the production of oxidized low-density lipoprotein (LDL). These studies establish CBD as both an important experimental tool and as a lead compound for pharmaceutical development. In this review, the author further discusses the potential uses of CBD and its derivatives in future medicines.<br>

著者

鈴木 信也 村山 悠佳 杉山 恵理花 関山 正夫 佐藤 均

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.7, pp.829-842, 2009

被引用文献数

8 3

---

We established dose estimation formulae for renal-excretion drugs using the glomerular filtration rate (GFR), tubular secretion clearance (Sc), and unbound fraction of drug in plasma (fp) as a renal function index of physiological development in neonates and infants not more than 2 years of age. A dose ratio of (D_C/D_A)=clearance ratio of (CL_C/CL_A)≅(fp_C·GFR_C)/(fp_A·GFR_A) for neonates and infants/adults was applied to drugs with fp·GFR>Sc, while D_C/D_A=CL_C/CL_A≅(β·BSA_C+fp_C·GFR_C)/(β·BSA_A+fp_A·GFR_A) was applied to drugs with Sc>fp·GFR using the coefficient of each drug (β) and body surface area (BSA). Validity of the estimation formulae was investigated in drugs with fp·GFR>Sc such as vancomycin (VCM), arbekacin (ABK), fosfomycin (FOM) and norfloxacin (NFLX), and in drugs with Sc>fp·GFR such as digoxin (DGX) and amoxicillin (AMPC). First, we compared the clearance ratio (CL_C/ CL_A) of VCM, ABK, and DGX estimated by our method with those calculated using the Japanese population clear- ance values and those estimated allometrically (BSA_C/BSA_A). Next, we compared the established doses of all drugs investigated with the doses for neonates and infants calculated from the conventional dose estimation methods for children and our estimation formulae, and evaluated our method. As a result, favorable consistency was observed in the CL ratio for all drugs, and the doses of VCM, FOM, NFLX and AMPC calculated from our estimation formulae approximated the established doses. In conclusion, the validity of the dose estimation method using pharmacokinetic factors related to physiological development (i.e., GFR, fp, Sc) for renal-excretion drugs in neonates and infants was demonstrated.<br>

著者

佐藤 倫広 松本 章裕 原 梓 岩森 紗希 小原 拓 菊谷 昌浩 目時 弘仁 保坂 実樹 淺山 敬 高橋 信行 佐藤 博 眞野 成康 今井 潤 大久保 孝義

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.12, pp.1347-1355, 2014 (Released:2014-12-01)

参考文献数

18

被引用文献数

1 5

---

Encouraging self-medication is expected to reduce healthcare costs. To assess the current situation of self-medication practices in the general population, we conducted a questionnaire survey regarding the use of over-the-counter (OTC) medications or dietary supplements in 1008 participants (37% men; mean age, 64±13 years) from Ohasama, a rural Japanese community. A total of 519 (52%) participants used OTC medications or dietary supplements, with common cold medication (36%) and supplements (28%) such as shark cartilage products representing the most common choices. Stepwise logistic regression showed female gender, a higher frequency of visits from a household medicine kit distributor, dyslipidemia, and lower home systolic blood pressure levels as predictors for the use of such materials (chi-square values: 25.3, 12.6, 7.0, and 4.6, respectively; all p<0.03). Stratifying the participants according to the use of antihypertensive treatment showed a negative association between systolic blood pressure and the use of OTC medications or supplements only in participants being treated for hypertension. These results suggest that although the adoption rate of self-medication in Japan can be increased in rural areas, it may remain lower in urban areas. The present study clarifies the factors associated with the use of OTC medications or dietary supplements and indicates that appropriate self-medication practices might improve the control of hypertension, particularly in patients undergoing antihypertensive treatment.

著者

荒井 基晴 前田 一人 佐藤 宏樹 三木 晶子 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

pp.16-00041, (Released:2016-06-27)

参考文献数

8

被引用文献数

2

---

We created a draft of new patient information leaflets to ensure patients’ proper use of drugs and to highlight safety issues and improvement plans extracted and proposed by small group discussions (SGD) with pharmacists. A total of 3 SGDs (participants: 15 pharmacists) were conducted with the aim of improving patient information leaflets for oral diabetes drugs. First, the disadvantages and advantages of the current instructions as well as requests for ideal patient information leaflets were obtained from participants.Conventional patient information leaflets that could be improved were useful to understand drug efficacy, adverse effects, and instructions for daily consumption of medicines, and to encourage patients to re-check drugs at home and inform their family of the measures to be taken in the case of adverse effects from the standpoint of patients. However, some disadvantages arose; for example, the instructions were difficult to read because of small lettering and illustrations and too much text. It was not tailored for individual patients, and descriptions about serious adverse effects caused patients much anxiety. Therefore, we have created a draft of new patient information leaflets with diabetes that are simpler and easier to understand and use concise wording and illustrations that are impactful.

著者

朴 恵林 三木 晶子 佐藤 宏樹 馬来 秀行 浅井 康平 小西 ゆかり 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.136, no.6, pp.913-923, 2016 (Released:2016-06-01)

参考文献数

6

被引用文献数

7

---

We conducted a workshop that aimed to clarify problems with care workers supporting medication use in nursing homes, to propose measures for solving these problems, and to raise awareness of these problems among care workers. Eighteen care workers from different fee-based elderly nursing homes were enrolled in the workshop, and divided into four groups. The participants in these groups identified the issues based on their experiences regarding medication-related incidents, and discussed related problems and viable measures using the KJ method. The issues identified by each group were “dropping a medication”, “wrong resident”, “refusal to take medication”, and “confusion”. To resolve these problems, the participants recommended: “conducting study sessions or testing of manuals and medication knowledge”, “strengthening monitoring systems”, “enhancing information sharing”, etc. The involvement of pharmacists was hardly mentioned, despite the workshop being designed for “medication assistance”. A post-workshop questionnaire revealed that 88.9% of the participants acknowledged an increased awareness of safe assistance in the use of medication. A follow-up questionnaire, distributed approximately seven months after the workshop, revealed that 82.4% of participants applied the experience and knowledge they learned at the workshop to their work. The workshop seemed to raise awareness and lead to preventive measures for safe medication assistance. Communication between care workers and other health care professionals, such as pharmacists, is important to designing and implementing safe medical care in nursing homes.

著者

福島 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.136, no.5, pp.717-719, 2016 (Released:2016-05-01)

参考文献数

9

被引用文献数

1

---

Keio University Faculty of Pharmacy opened an insurance pharmacy on its campus in 2001. This pharmacy was opened with the objectives of 1) educating pharmacists to serve the regional community; 2) heightening students' motivation; and 3) providing practical education geared to the needs of actual healthcare settings. Since my appointment as director in 2003, I have led various initiatives to determine an ideal business model for a university pharmacy. This paper reports these initiatives and discusses the mission and future prospects of university pharmacies. In terms of education, all 4th-year students provide medication guidance to simulated patients at our university pharmacy counters, and are briefed by pharmacists about pharmacy administration and dispensing activities. Over three periods each academic year, trainees from other universities have been accepted for long-term on-site training. Students also work at local facilities for elderly persons to learn how to effectively communicate with this demographic and to better understand their unique pharmacokinetic profiles, impaired QOL, etc. Students can also participate in health promotion and drug education courses for regional residents, and support their self-medication. Pharmacies are important points of contact with local communities where residents' lives can be medically monitored. It is important for pharmaceutical universities to operate their own pharmacies in order to determine and stay abreast of the evolving challenges society expects pharmaceutical science to address. University pharmacies need to become models for general community pharmacies.

著者

関口 慶二

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.81, no.5, pp.669-674, 1961-05-25 (Released:2010-02-19)

参考文献数

9

被引用文献数

8

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Thermal analysis was carried out on 26 kinds of binary systems, having caffeine as one component and various carboxylic acids as the other. Molecular compounds were formed by caffeine with o-, m-, and p-hydroxybenzoic acid, gallic acid, m-me-thoxybenzoic acid, m-nitrobenzoic acid, o-, m-, and p-aminobenzoic acid, phenylacetic acid, malonic acid, oxalic acid dihydrate, and maleie acid. Caffeine did not form a molecular compound with benzoic and phthalic acids. Comparison of the result of thermal analysis and the report of Higuchi and others regarding caffeine complex in aqueous solution suggested that there is some difference in the behavior of caffeine between anhydrous state and in aqueous solution.

著者

生田目 一寿

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.231-236, 2016 (Released:2016-02-01)

参考文献数

5

---

Neglected tropical diseases (NTDs) are an extremely important issue facing global health care. To improve “access to health” where people are unable to access adequate medical care due to poverty and weak healthcare systems, we have established two consortiums: the NTD drug discovery research consortium, and the pediatric praziquantel consortium. The NTD drug discovery research consortium, which involves six institutions from industry, government, and academia, as well as an international non-profit organization, is committed to developing anti-protozoan active compounds for three NTDs (Leishmaniasis, Chagas disease, and African sleeping sickness). Each participating institute will contribute their efforts to accomplish the following: selection of drug targets based on information technology, and drug discovery by three different approaches (in silico drug discovery, “fragment evolution” which is a unique drug designing method of Astellas Pharma, and phenotypic screening with Astellas' compound library). The consortium has established a brand new database (Integrated Neglected Tropical Disease Database; iNTRODB), and has selected target proteins for the in silico and fragment evolution drug discovery approaches. Thus far, we have identified a number of promising compounds that inhibit the target protein, and we are currently trying to improve the anti-protozoan activity of these compounds. The pediatric praziquantel consortium was founded in July 2012 to develop and register a new praziquantel pediatric formulation for the treatment of schistosomiasis. Astellas Pharma has been a core member in this consortium since its establishment, and has provided expertise and technology in the area of pediatric formulation development and clinical development.

著者

齋藤 充生 山本 美智子

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.136, no.2, pp.243-244, 2016 (Released:2016-02-01)

著者

杉野 雅浩 三上 充宏 石原 智樹 細谷 治 從二 和彦

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.135, no.8, pp.977-985, 2015 (Released:2015-08-01)

参考文献数

23

被引用文献数

2

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A generic drug is defined as a drug product that is comparable to a brand name drug in terms of dosage, form, strength, route of administration, quality, performance characteristics, and indicated use. Generic drugs for topical use, in the case of sheet-like products, are required to be the same as the original drug in terms of application area and dosage form. The composition of such generic drug formulations may differ from that of the original product. The adhesive of any pharmaceutically-active tape that directly contacts the skin plays a role in delivering the active ingredient into the skin, and affects the sensation and ease of handling. Therefore, adhesives are an important ingredient in these products. Thus, the aim of this study was to characterize original and generic lidocaine tape products, and to evaluate the adhesive properties of each. The tack force, peel strength and shear adhesion were measured as adhesive properties. In addition, in vitro drug releasing profiles and skin permeation profiles of the products were evaluated. In vivo transdermal absorption was also evaluated to predict the possibility of adverse effects. Adhesive properties differed among the three analyzed products. These differences may have been caused by differences in the adhesives. Drug-releasing profiles and skin permeation profiles also differed among the three products, even though the pharmacokinetics were not significantly different. By obtaining an adequate understanding of the characteristics of original and generic products, we will be able to provide better tailor-made medications for drug therapies for patients.

著者

赤川 信一郎 森川 則文 池田 佳代 岡崎 照夫 高橋 俊輔

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.2, pp.175-179, 2015 (Released:2015-02-01)

参考文献数

6

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A strategy named “Japan is back” adopted in June 2013 specifies that pharmacies shall be regarded as community-based places where health-related information is provided, and the public shall be encouraged to use the services of pharmacies and pharmacists who can advise on health and appropriate use of over-the-counter (OTC) drugs, and promote self medication. In Japan there are approximately 55000 pharmacies and 260000 pharmacists, and community residents are recommended to use these resources. As advisors on healthcare in the community, pharmacists are required to make judgments regarding drug use in individuals performing self medication and using OTC drugs in consideration of their symptoms and level of understanding of their health conditions, and recommend that they consult a medical center if necessary. To meet these requirements pharmacists need to have the skills to monitor each individual's lifestyle, behavior, and environment as well as trends in society, and assess their health status. However, education that allows pharmacists to practice such skills remains insufficiently developed. We consider that to be able to detect diseases early among community residents and appropriately support them using pharmacotherapy, it is very important to train pharmacists to do the following at pharmacies: 1) determine individuals who should be treated early using symptomatologic skills; 2) promote public awareness of disease; and 3) perform biochemical examination (blood is collected by fingerprick promptly to obtain biochemical data) in cooperation with the Department of Clinical Pharmacotherapy, Faculty of Pharmaceutical Sciences, Hiroshima University.

著者

韓 立坤 森本 千恵 蔚 ろん海 奥田 拓道

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.125, no.5, pp.449-453, 2005 (Released:2005-05-01)

参考文献数

9

被引用文献数

11 28

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The antiobesity effects of Coleus forskohlii were investigated in ovariectomized (ovx) rats. Eight-week-old female Wistar rats were assigned to four groups: a sham-operated group fed the control diet (MF, sham-m) ; an ovx-m group fed the control diet; a sham-operated group fed the control diet containing 50 g/kg of Coleus forskohlii extract (sham-c) ; and an ovx-c group fed the control diet containing 50 g/kg of Coleus forskohlii extract. The body weight, adipose tissues, and cell diameter were investigated in ovx rats after Coleus forskohlii extract treatment. Administration of Coleus forskohlii extracts reduced body weight, food intake, and fat accumulation in ovx rats. Our results suggest that Coleus forskohlii may be useful in the treatment of obesity.

著者

山田 英之 武田 知起 古賀 貴之 石井 祐次

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.4, pp.529-535, 2014 (Released:2014-04-01)

参考文献数

28

被引用文献数

3

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The sexual differentiation of animal fetuses and infants needs stimuli by sex steroids, which are produced in their own gonads, during a short window (‘critical period’) of pre- and post-natal periods. Our laboratory has conducted a series of studies focusing on the damage to next generations by dioxins. When pregnant rats are exposed to a prototype of dioxin, 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD; 1 μg/kg), sexual immaturity such as defects in copulation behavior as well as growth retardation emerges in their pups. We have provided evidence that such disorders are evoked, if not all, from a transient reduction in the gonadal synthesis of sex steroids in fetuses/infants during the critical period. Our studies also revealed that TCDD initially reduces the pituitary expression of luteinizing hormone (LH) to exert the effect on steroidogenesis. Several mechanisms seem to be involved in a TCDD-induced reduction in LH expression. For example, a change in epigenetic regulation in the pituitary and impaired energy production in the hypothalamus are suggested to contribute to the above reduction. Current our study has demonstrated that a transient reduction in the pituitary-gonad axis fixes the lowered expression of hypothalamic gonadotropin-releasing hormone, resulting in defects in sexual behavior. Through these topics, we discuss the role of the critical period in differentiation and development.