YAKUGAKU ZASSHI
Online ISSN : 1347-5231
Print ISSN : 0031-6903
ISSN-L : 0031-6903
127 巻 , 12 号
選択された号の論文の24件中1~24を表示しています
誌上シンポジウム
  • 東 達也, 浜瀬 健司
    2007 年 127 巻 12 号 p. 1895-1896
    発行日: 2007/12/01
    公開日: 2007/12/01
    ジャーナル フリー
  • 木下 英司, 木下 恵美子, 小池 透
    2007 年 127 巻 12 号 p. 1897-1913
    発行日: 2007年
    公開日: 2007/12/01
    ジャーナル フリー
      Protein phosphorylation is one of the most important post-translational modifications. Organisms utilize this reversible reaction of proteins to control many cellular activities, including signal transduction, apoptosis, gene expression, cell cycle progression, cytoskeletal regulation, and energy metabolism. Abnormal protein phosphorylation is deeply related to carcinogenesis and neuropathogenesis. Methods for monitoring the phosphorylation status of proteins are, thus, very important with respect to the evaluation of diverse biological and pathological processes. Recently, we reported that a dinuclear metal complex of 1,3-bis[bis(pyridin-2-ylmethyl)-amino]propan-2-olato acts as a novel phosphate-binding tag molecule, Phos-tag, in an aqueous solution under physiological conditions. The Phos-tag has a vacancy on two metal ions that is suitable for the access of a phosphomonoester dianion (R-OPO32-) as a bridging ligand. The resulting 1:1 phosphate-binding complex, R-OPO32--(Phos-tag)3+, has a total charge of +1. A dinuclear zinc(II) complex (Zn2+-Phos-tag) strongly binds to phenyl phosphate dianion (Kd=2.5×10-8 M) at a neutral pH. The anion selectivity indexes against SO42-, CH3COO-, Cl-, and bisphenyl phosphate monoanion at 25°C are 5.2×103, 1.6×104, 8.0×105, and>2×106, respectively. A manganese(II) homologue (Mn2+-Phos-tag) can also capture the R-OPO32- anion, such as phosphoserine, phosphotyrosine, and phosphohistidine, at an alkaline pH. By utilizing the Phos-tag molecule and its derivatives, we developed convenient and reliable methods for the detection of phosphorylated proteins. We believe that our Phos-tag technology will result in great progress in phosphoproteomics.
  • 梅澤 直樹, 秋田 昌二, 鴨東 美絵, 樋口 恒彦
    2007 年 127 巻 12 号 p. 1915-1925
    発行日: 2007/12/01
    公開日: 2007/12/01
    ジャーナル フリー
      Recently, the fluorometric detection of biomacromolecules has attracted much attention. In this paper, we report the development of two new techniques utilizing the chemical properties of amino acids or peptides: 1) a fluorescence assay for serine/threonine kinase activity; and 2) “turn-on” fluorescent probes for protein labeling, which could be useful for bioimaging. To develop the novel kinase assay, we utilized the chemical reactivity of phosphorylated serine or threonine. Phosphorylated peptide on resin was successfully labeled fluorescently via base-mediated β-elimination, followed by Michael addition with novel coumarin derivatives. Protein kinase A and casein kinase I activities were detectable with our method. Also, this method was confirmed to be applicable for kinase inhibitor screening. For the development of the novel protein labeling technique, the selective interaction between “His-tag (His6)” and “metal ion nitrilotriacetic acid (NTA) complex” was utilized. This interaction is useful for protein purification and immobilization. We designed fluorescent probes composed of a fluorophore and Ni2+ or Co2+-NTA complex. These probes were found to be weakly fluorescent as expected. When His-tag peptide was added, these probes became brightly fluorescent. On the other hand, these probes remained non fluorescent with the addition of angiotensin I (H-Asp-Arg-Val-Tyr-Ile-His-Pro-Phe-His-Leu-OH). These probes will be powerful tools for the bioimaging of target proteins.
  • 古地 壯光, 本間 浩
    2007 年 127 巻 12 号 p. 1927-1936
    発行日: 2007年
    公開日: 2007/12/01
    ジャーナル フリー
      Proteins are subject to various types of spontaneous modifications that can disrupt their structures with sometimes adverse affects on biological activity. The formation of L-isoaspartyl (or D-aspartyl) residues, through either the deamidation of asparagine or dehydration of aspartate, is one of the most frequent types of deterioration occurring under physiological conditions. Protein L-isoaspartate/D-aspartate o-methyltransferase (PIMT) is a conserved and ubiquitous enzyme that participates in the repair of various isomerized proteins. PIMT catalyzes the transfer of the methyl group of S-adenosyl-L-methionine onto the α-carboxyl group of an L-isoaspartyl (or the β-carboxyl group of an D-aspartyl) residue, which initiates the conversion of this residue to an L-aspartyl residue. PIMT-deficient mice have been shown to die at a mean age of 42 days from progressive epileptic seizures with grand mal and myoclonus. Although PIMT-deficiency clearly leads to the accumulation of isomerized proteins, it is currently unclear how this causes progressive epilepsy in PIMT-deficient mice. As a first step towards understanding this, we developed a new assay to measure PIMT activity in cell lysates. Additionally, we isolated PIMT knockdown cells from HEK293 cells that were stably transfected with a PIMT small interfering RNA expression vector. PIMT activities were significantly decreased in the PIMT knockdown cells, and analysis of the transfectants revealed that MEK and ERK were hyperactivated after cell stimulation with epidermal growth factor (EGF). These results indicate that the ability to repair L-isoaspartyl-(or D-aspartyl-) containing proteins is important for the maintenance of normal MEK-ERK signaling.
  • 向 高弘
    2007 年 127 巻 12 号 p. 1937-1945
    発行日: 2007/12/01
    公開日: 2007/12/01
    ジャーナル フリー
      In vivo radiopharmaceuticals have two different uses - for nuclear diagnostic imaging and for internal radiation therapy. For nuclear diagnostic imaging, it is necessary to make the difference of radioactivity levels between in the target regions and in the other regions at an early time after administration. For internal radiation therapy, a more selective accumulation of the radioactivity to the target regions is required to minimize an adverse effect. In order to achieve the highly selective accumulation of in vivo radiopharmaceuticals, it is necessary to find an appropriate target molecule in the first place and design a compound which can recognize the target molecule and stably label it with radionuclide. There are several proposed approaches to chemical design for this purpose. However, even with the specific recognition and stable radiolabel, targeted imaging and therapy are not necessarily achieved. We have been developing in vivo radiopharmaceuticals based on a chemical design called “bifunctional radiopharmaceutical.” Bifunctional radiopharmaceuticals have the recognition site of the target molecule and binding site for the radionuclide independently in one molecule. This review summarizes our examples of chemical design of in vivo radiopharmaceuticals to achieve the targeted imaging and therapy.
  • 中西 剛
    2007 年 127 巻 12 号 p. 1947-1948
    発行日: 2007年
    公開日: 2007/12/01
    ジャーナル フリー
  • 角 大悟, 熊谷 嘉人
    2007 年 127 巻 12 号 p. 1949-1956
    発行日: 2007/12/01
    公開日: 2007/12/01
    ジャーナル フリー
      Prolonged exposure of humans to ambient particulate matter such as diesel exhaust particles (DEP) induces a variety of adverse health effects including cardiovascular diseases, asthma and cancer. Polycyclic aromatic hydrocarbons (PAHs) and their derivatives in DEP are thought to be potential candidates for the deleterious effects of DEP. We have identified 1,2-naphthoquinone (1,2-NQ) as a novel PAH quinone that contaminates DEP. Because 1,2-NQ is covalently bound to macromolecules through reactive thiols (thiolate ions), our rationale was that cellular proteins modified by 1,2-NQ seem to act as a redox-sensor and thus the interaction of thiol proteins with 1,2-NQ may disrupt their functions. To address our hypothesis, we prepared specific antibody against 1,2-NQ bound to proteins. In this review, we introduce an inhibitor of κB kinaseβ (IKKβ) and protein tyrosine phosphatase 1B (PTP1B) as target molecules for 1,2-NQ. Although IKKβ activates transcription factor NF-κB and PTP1B negatively regulates the receptor-protein tyrosine kinase, such as epidermal growth factor receptor (EGFR) in cells, covalent modification of these proteins caused by 1,2-NQ results in inhibition of NF-κB activity and transactivation of EGFR.
  • 木村 朋紀
    2007 年 127 巻 12 号 p. 1957-1965
    発行日: 2007年
    公開日: 2007/12/01
    ジャーナル フリー
      Chromium exists in many different oxidation states in the environment, Cr(VI) and Cr(III) being the most stable forms. Chromium has been known for over 100 years to be a human carcinogen. The greatest risk of cancer from chromium exposure is associated with Cr(VI). Cr(VI) enters cells via the sulfate anion transporter system and is reduced to intermediate oxidation states, such as Cr(V) and Cr(IV), in the process of forming stable Cr(III) forms. It is known that Cr(VI) affects expression of various genes. Metal responsive element-binding transcription factor-1 (MTF-1) is involved in sensing heavy metal load and the induced transcription of several protective genes, including metallothionein (MT)-I, MT-II, zinc transporter-1, and γ-glutamylcysteine synthetase. Cr(VI) inhibits zinc-induced MT transcription via modifying transactivation potential of MTF-1. However, the molecular mechanism for the Cr(VI)-mediated inhibition of MTF-1 has not been fully elucidated. In this review, I briefly summarize the previous studies and discuss the current status of research on Cr(VI) toxicity and Cr(VI)-mediated inhibition against transcription.
  • 渡邉 肇
    2007 年 127 巻 12 号 p. 1967-1974
    発行日: 2007年
    公開日: 2007/12/01
    ジャーナル フリー
      Concern about the toxicity of chemicals released into the environment has been increasing recently. Many chemicals are suspected to have hazardous effects, but evaluation of their toxicity is still difficult and challenging. One of these difficulties is the presence of chemicals that are reported to have an adverse effect on organisms despite negative results in conventional toxicity tests. Thus, a new technique has been desired in order to evaluate the effects of chemicals, Recent advances in molecular biology have provided a technique for better understanding the responses of organisms to chemicals; this emerging field is known as toxicogenomics. Toxicogenomics is defined as an integration of genomics (transcriptomics, proteomics, metabolomics) and toxicology. For example, the DNA microarray can be used to explore the gene expression profiles (transcriptomics) of organisms in response to chemicals. Exposure to chemicals results in characteristic gene expression profiles, suggesting that the DNA microarray can be used to evaluate chemical effects. Toxicogenomics is also expected to be useful in gaining a mechanistic understanding of these effects. Although it still has some limitations, this technique can be developed to assess chemicals.
総説
  • 中西 勤
    2007 年 127 巻 12 号 p. 1975-1996
    発行日: 2007/12/01
    公開日: 2007/12/01
    ジャーナル フリー
      This review describes chemical and biological studies on natural products achieved by the author for the latest 47 years and its main contents are composed of the following researches of the eight sections, entitled 1) Hopane-type triterpenes from a lichen, Parmelia leucotyliza, 2) Spirostanol and frostanol glycosides from Metanarthecium luteo-viride (Liliaceae), 3) Selective reduction of double bonds: preparation of 22,23-dihydroergosterol from ergosterol, 4) Compositions and structures of fragrant sesquiterpenes from several types of agarwoods, 5) Triterpenes and other components from Meliaceous plants, 6) Constituents of seeds of crude drugs and medicinal plants, 7) Hopane-type triterpene glycosides from a fern, Diplazium subsinuatum, 8) Search and structural elucidation of biologically active components from American plants obtained from United States of America (Oregon and California), Mexico, Guatemala, and Honduras. In this review, many classes of natural products, i.e., terpenoids (mono-, sesqui-, di-, and triterpenoids), steroids, glycosides, saponins, tannins, phenylpropanoids, lignans, flavonoids (flavones, flavonols, flavanones, biflavones, flavan-3-ols, etc.), etc. are dealt with and referred to.
  • 國友 勝
    2007 年 127 巻 12 号 p. 1997-2014
    発行日: 2007/12/01
    公開日: 2007/12/01
    ジャーナル フリー
      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.
  • 加藤 大
    2007 年 127 巻 12 号 p. 2015-2025
    発行日: 2007/12/01
    公開日: 2007/12/01
    ジャーナル フリー
      It is becoming increasingly important to separate mixed samples, such as bio- and environmental samples. For the analysis of a target compound in a mixed sample, a highly efficient and selective separation method is required. We have developed columns of high resolution, very selective columns, and highly efficient analytical methods using integrated techniques and biomolecules. These developed methods save analytical time, sample volume, etc. We are now interested in nano scale materials which many people are now focusing on. Although excellent nano materials have been developed by many researchers, there are few efficient separation, purification or evaluation methods for these compounds. In this review, we introduce our recent achievements concerning the separation of nano compounds.
一般論文
  • 高柳 理早, 渡邊 昌之, 日野原 芳美, 鈴木 優司, 横山 晴子, 大関 健志, 安藤 利亮, 土橋 朗, 山田 安彦
    2007 年 127 巻 12 号 p. 2027-2033
    発行日: 2007年
    公開日: 2007/12/01
    ジャーナル フリー
      We established a network meeting system program and used it to review a prior pharmaceutical practice training session. Pharmacists at Tokai University Hachioji Hospital gave lectures about dispensing and other tasks performed by clinical pharmacists to third-year undergraduate students at Tokyo University of Pharmacy and Life Sciences. After the lectures, discussions were held using the network meeting system, after which a questionaire was completed by the students. The questionaire was answered by 530 students, of whom approximately 90% expressed interest in the program, 80% noted approval of the media used in the system, and 94% thought that the program was useful. Thus, we concluded that the students were motivated by the program to remember what they had learned in the lectures. We also found that the quality of data communication had an effect on the interests and motivation of the students. Based on their evaluation of the media, it was considered that improvements in communication regarding the system were necessary, though the evaluation of the utility of the program was not influenced by the quality of data communication. As a result, we concluded that our network meeting system program was useful to review prior learning of pharmaceutical practice.
  • 加藤 洋美, 吉井 美智子, 小澤 光一郎
    2007 年 127 巻 12 号 p. 2035-2044
    発行日: 2007/12/01
    公開日: 2007/12/01
    ジャーナル フリー
      In the present study, we tested three kinds of sleeping drugs, consisting mainly of triazolam, brotizolam, and flunitrazepam, to compare the drug efficacy of generic drugs with that of original drugs. After these drugs were administered orally to mice, drug efficacy was evaluated in terms of ambulation, onset time of sleep, and duration of sleep in the open field test. For all kinds of sleep-inducing drugs, the drug efficacy of most generic drugs is not necessarily equal to that of the original drug. The main reason for the difference appears to be due to differences in the rate of absorption of the main drug. Any other differences between an original drug and a generic drug are caused by drug additives, the crystal form of the main drug, the formulation, and so on. In this study, the formulation was not the reason for the differences because all of the drugs were pulverized in a mortar and had no special coating. The drug additives for all the drugs are listed and the drug efficacy compared. Unfortunately, the information was not sufficient to shed any light on the differences in drug efficacy. For effective drug therapy, more information on drug additives should be provided.
  • 小林 寛子, 小原 拓, 高橋 則男, 高橋 武, 猪狩 有紀恵, 及川 卓也, 齋藤 真一郎, 大久保 孝義, 今井 潤, 高橋 將喜
    2007 年 127 巻 12 号 p. 2045-2050
    発行日: 2007年
    公開日: 2007/12/01
    ジャーナル フリー
      Calcium channel blockers are most commonly used in hypertensive patients in Japan. However, information on the efficacy and safety of generic calcium channel blockers is insufficient. The objective of the present study was to retrospectively evaluate the efficacy and safety of manidipine hydrochloride in 21 essential hypertensive patients (mean age; 70.6±10.6 years, male/female; 14/7) in Sendai Postal Services Agency Hospital who were switched (substituted) from a brand product (Calslot®) to a generic product (Manidip®). For this retrospective study, we used data from patient medical records and drug prescription information. Data from patients who were taking both types of manidipine hydrochloride, whose regimen were not changed for > 6 months before and after switching, and who provided informed consent were included in the analysis. Control values of blood pressure were not significantly different between before and after substitution (systolic/diastolic; from 137.9±9.1/78.7±5.4 mmHg to 137.3±9.1/77.8±6.3 mmHg, p=0.73/p=0.36). The level of patient compliance for the antihypertensive drugs was also not different between before and after substitution (from 94.0±8.8% to 93.1±9.6%, p=0.72). There were 8 cases of adverse effects before substitution and 4 after substitution. No patient stopped taking the generic drug due to an adverse effect. In conclusion, significant differences in the efficacy, safety, and patient compliance were not observed between the brand product and generic product among patients who were switched from the brand product to the generic product.
  • 網岡 克雄, 和田 育男, 古田 禎之
    2007 年 127 巻 12 号 p. 2051-2055
    発行日: 2007/12/01
    公開日: 2007/12/01
    ジャーナル フリー
      The interactions between miglitol, an α-glucosidase inhibitor, and six adsorbents (carbon spheres, cholestyramine, colestimide, sevelamer hydrochloride, calcium polystyrene sulfonate, and sodium polystyrene sulfonate) were investigated in vitro. Miglitol corresponding to the minimum dose and adsorbents corresponding to the maximum dose were incubated at 37°C for 180 min in solutions of pH 1.2 (gastric pH condition) and pH 6.8 (enteric pH condition), with and without the presence of carbohydrates, which were added to observe the effects on food adsorption. The adsorption ratio of miglitol to carbon spheres was 13.6% and 0% in pH 1.2 solution and 86.4% and 5.0% in pH 6.8 solution without and with the presence of carbohydrates, respectively. Thus, the adsorption ratio was higher in pH 6.8 solution. Adsorption of miglitol to calcium polystyrene sulfonate was nearly the same, 15.0-21.9%, at both pH. The adsorption ratio of miglitol to sodium polystyrene sulfonate was 43.4% and 45.5%, respectively, in pH 1.2 solution without and with carbohydrates. In the pH 6.8 solutions, however, the respective adsorption ratios were low (5.2% and 11.3%). Miglitol did not adsorb to cholestyramine, sevelamer hydrochloride or colestimide under any pH condition examined. The above results suggest that miglitol adsorbs to carbon spheres and polystyrene sulfonic acid cation exchange resins. However, considering that miglitol is taken just before eating and thus exists in gastointestinal fluids together with food, and that the site of its effect is the upper small intestine, the interactions between miglitol and these adsorbents will most likely not be a problem.
  • 櫻井 雅人, 尾関 有一, 安藤 正樹, 岡本 浩一, 檀上 和美
    2007 年 127 巻 12 号 p. 2057-2063
    発行日: 2007/12/01
    公開日: 2007/12/01
    ジャーナル フリー
      One-Step Dry-Coated tablets (OSDrC) of a colon-targeting drug were prepared using Eudragit L 100-55 (Eud-L) and chitosan (Chit) as the outer layer. Lag time in the 1st fluid, which simulated the stomach, was affected by differences in the pores occurring as a result of Chit dissolution. The dissolution rate of Chit was decreased by the addition of Eud-L. On the other hand, lag times in phosphate buffer (pH 7.4) simulating the small intestine, and in the 2nd fluid simulating the colon, were affected by differences in the pores occurring as a result of Eud-L dissolution and Chit swelling. The lag time of OSDrC with an outer layer of Eud-L:Chit at a ratio of 3:1 in each test medium was greater than the gastric emptying time in the 1st fluid and the small intestine transit time in phosphate buffer (pH 7.4). Furthermore, lag times were similar when test media were changed sequentially. Therefore, it is possible to deliver colon-targeting drugs as OSDrC with an outer layer of Eud-L:Chit at 3:1.
  • 座間味 義人, 高取 真吾, 小山 敏広, 合田 光寛, 岩谷 有希子, 土井 志真, 川崎 博己
    2007 年 127 巻 12 号 p. 2065-2073
    発行日: 2007/12/01
    公開日: 2007/12/01
    ジャーナル フリー
      Propolis, a honeybee product, contains a variety of biologically active substances. The present study was designed to investigate the effects of propolis on insulin resistance induced by fructose-drinking rats (FDR; type 2 diabetic animal model). Male Wistar rats (6 weeks old) received 15% fructose solution in drinking water for 8 weeks. FDR showed significant increases in plasma levels of insulin, Homeostasis Model Assessment ratio (HOMA-R, an index of insulin resistance), body weight, and systolic blood pressure but not blood glucose levels, when compared with control rats. Brazilian propolis extract (100 and 300 mg/kg, p.o.) treatment for 8 weeks significantly decreased the plasma level of insulin, HOMA-R, and body weight, increased plasma triglyceride levels without affecting blood glucose and total cholesterol levels, and tended to decrease systolic blood pressure. In isolated and perfused mesenteric vascular beds of FDR, propolis treatment resulted in a significant reduction of sympathetic nerve-mediated vasoconstrictor response to periarterial nerve stimulation (PNS; 8 Hz) and tended to increase the calcitonin gene-related peptide (CGRP) nerve-mediated vasodilator response to PNS, compared with those in untreated FDR. However, propolis treatment did not significantly affect norepinephrine-induced vasoconstriction and CGRP-induced vasodilation. These results suggest that propolis could be an effective functional food to prevent the development of insulin resistance.
ノート
  • 恩田 光子, 奥田 勅子, 高坂 直宏, 高橋 伸明, 松浦 正佳, 山口 雄治, 山田 理花
    2007 年 127 巻 12 号 p. 2075-2078
    発行日: 2007/09/18
    公開日: 2007/12/01
    ジャーナル フリー
      Our group conducted a Medication Safety Culture Building Drive, enlisting the cooperation of pharmacy patients to clarify obstacles and verify the effect of the measures implemented. Pharmacists at 38 community pharmacies instituted a 3-month trial period of rigorous prescription confirmation by checking filled prescriptions against the accompanying drug information (DI) in the presence of patients at pharmacy counters, whenever prescription drugs were dispensed. During the first month, 29 pharmacies reported carrying out the program with the rate of patient coverage was over 50%; while 8 others reported that rate of patient coverage was less than 50%. Factors standing in the way of checking filled prescriptions with the patients could be characterized as “physical conditions,” “prescription content,” or “patient attributes.” The measures devised to counter these obstacles all fell within the categories of “education of patients and pharmacists,” “advance arrangements made in preparation for checking,” “methods of checking and nature of items checked,” “checking procedure,” and “DI literature.” After three month, 34 pharmacies reported that the effort had been effective. During the three months, the average implementation rate (patient coverage rate) was improved from 92.5% in April to 96.5% in June (p<0.001). The specific qualitative effects listed below were among those mentioned in reports compiled from meetings. 1) Improvement of patients' and pharmacists' awareness regarding dispensing error prevention, 2) Increase in patients' interest in, and understanding of, their own prescription medications, 3) Increase in patients' understanding about the efforts and in number of patients cooperating with the effort.
  • 嵜山 陽二郎, 小宮山 靖, 塚田 秀夫
    2007 年 127 巻 12 号 p. 2079-2084
    発行日: 2007/12/01
    公開日: 2007/12/01
    ジャーナル フリー
      Animal pain testing is essential for the development of new analgesic drugs, where appropriate data analyses as well as appropriate multi-factorial design of experiments are necessary to obtain meaningful results in an efficient fashion. The tail withdrawal experiment is one of the pain tests in which a rhesus monkey is restrained in a chair from which its tail hangs free by so it can be immersed in warm water. The monkeys consistently kept their tails in 38-40°C water for an extended period of time, and thus, the data were censored at 120 sec. The effect of temperature on the tail withdrawal latency was evaluated using three monkeys with a randomized block design. The effect of morphine on the thermal sensitivity was also evaluated. A Friedman-type two-way analysis of variance (Mack-Skillings test) demonstrated that the effects of both temperature and the animals were significant. The effect of repeated measurement in one animal was not significant using the Friedman test, indicating that the significance of the effect of animals could be attributed to the difference in the intrinsic thermal sensitivity between animals. This method, together with a graphical approach, may prove to be valuable for assessing the sensitivity and reproducibility of an experimental condition, as well as the pharmacological effects of analgesic drugs.
  • 井上 千亜紀, 小暮 俊明, 鎌田 彩, 石原 美佳, 村岡 玲子, 辰見 明俊, 田中 邦佳, 竹下 治範, 濱口 常男, 多河 典子, ...
    2007 年 127 巻 12 号 p. 2085-2089
    発行日: 2007/12/01
    公開日: 2007/12/01
    ジャーナル フリー
      For the purpose of quality evaluation of commercially available magnesium oxide (MgO) tablets, we studied their acid neutralization and dissolution behaviors. The dissolution test was carried out by the paddle method in 1st fluid (pH 1.2). The dissolution amount of MgO from tablets was determined by chelatometric titration. The medium pH was periodically measured. The neutralization reaction in 750 ml of 1st fluid was markedly different between two kinds of commercial tablets. The pH of medium including Magmit® tablet reached 8.9 and the dissolution rate of MgO was 81.1% after 20 min. Contrariwise, the final pH of medium including Maglax® tablet was 2.5 and the dissolution rate of MgO was 77.1% after 60 min. These results indicate that the dissolution rate of MgO from tablets should be >81.1% to obtain significant acid neutralization action.
  • 堀川 俊二, 徳本 和哉, 要田 芳代, 川上 恵子, 只佐 宣子, 礒貝 明彦, 竹増 まゆみ, 伊東 明彦
    2007 年 127 巻 12 号 p. 2091-2095
    発行日: 2007/12/01
    公開日: 2007/12/01
    ジャーナル フリー
      Intellectual ability of self-administration plays a crucial role in a diabetes regimen. However, in many cases, self-administration is considered difficult, because of the impairment of activities of the individual's daily living (ADL), instrumental ADL and cognitive function. To assess comprehensive-geriatric-assessment (CGA) in elderly diabetic sufferers, 62 elderly inpatients and outpatients aged over 70 years were investigated. CGA includes Barthel index (BI), Mini-mental-state-examination (MMSE) and the Tokyo Metropolitan Institute of Gerontology index of competence (TMIGIC). The relation of ability to self-administer and CGA was examined. In oral therapy, there was significant difference between self-administration and non-self-administration in MMSE (p=0.0065), BI (p=0.0219) and TMIGIC (p=0.0053). Among these indexes, TMIGIC was the most sensitive index in oral therapy. In insulin therapy, there was also significant difference between self-administration and non-self-administration: MMSE (p=0.00042), BI (p=0.000019) and TMIGIC (p=0.0019). Among these indexes, BI was the most sensitive index in insulin therapy. It was suggested that CGA was useful to assess the ability of self-administration in elderly diabetic patients.
  • 武田 直仁, 竹内 烈, 春名 光昌
    2007 年 127 巻 12 号 p. 2097-2103
    発行日: 2007/09/18
    公開日: 2007/12/01
    ジャーナル フリー
      In order to develop an e-learning system that promotes self-learning, lectures and basic operations in laboratory practice of chemistry were recorded and edited on DVD media, consisting of 8 streaming videos as learning materials. Twenty-six students wanted to watch the DVD, and answered the following questions after they had watched it: “Do you think the video would serve to encourage you to study independently in the laboratory practice?” Almost all students (95%) approved of its usefulness, and more than 60% of them watched the videos repeatedly in order to acquire deeper knowledge and skill of the experimental operations. More than 60% answered that the demonstration-experiment should be continued in the laboratory practice, in spite of distribution of the DVD media.
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