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130 巻, 3 号
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誌上シンポジウム
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西田 基宏2010 年 130 巻 3 号 p. 279-280
発行日: 2010年
公開日: 2010/03/01
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白川 久志, 中川 貴之, 金子 周司2010 年 130 巻 3 号 p. 281-287
発行日: 2010/03/01
公開日: 2010/03/01
ジャーナル フリーGlial cells are abundant in the CNS and play diverse roles in the regulation of neuronal activity, vascular function, and gliotransmitter release, whereas pathologically activated glial cells have been reported to disturb brain function in conjunction with Ca2+ signaling, however there is no enough explanation for a unique Ca2+ entry. Transient receptor potential (TRP) superfamily comprises a group of non-selective cation channels that open in response to divergent stimuli in their environment. Although TRP channels are widely distributed in the mammalian brain, their roles remain to be elucidated. Here we provide an overview of the roles of TRP channels in pathophysiological processes, especially focusing on TRPC3 and TRPV4 channels in glial cells. Using rat cortical astrocytes, we found that TRPC3 was upregulated by thrombin via Ca2+ signaling through TRPC3 itself. Thrombin also upregulated S100B, a marker of reactive astrocytes, and increased cell proliferation, both of which were inhibited by Ca2+ signaling blockers and specific knockdown of TRPC3 using siRNA, suggesting that TRPC3 contributes to the pathological activation of astrocytes in part through a feed-forward upregulation of its own expression. Moreover, we found that TRPV4 stimulation by its agonist 4α-PDD suppressed LPS-induced microglial activation while TRPV4 mRNA was downregulated in LPS-treated cultured rat microglia. These results suggest that TRP channels play pivotal roles in the process of astrocytic and microglial activation.
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富永 真琴2010 年 130 巻 3 号 p. 289-294
発行日: 2010/03/01
公開日: 2010/03/01
ジャーナル フリーTRP channels are well recognized for their contributions to sensory transduction, responding to a wide variety of stimuli including temperature, nociceptive stimuli, touch, osmolarity and pheromones. In particular, the involvement of TRP channels in nociception has been extensively studied following the cloning of the capsaicin receptor, TRPV1. Painful diabetic peripheral neuropathy is described as a superficial burning pain, and it is one of the most commonly encountered neuropathic pain syndromes in clinical practice. We found that hypoxic and high glucose conditions commonly observed in diabetes potentiate TRPV1 activity without affecting TRPV1 expression both in native rat sensory neurons and HEK293 cells expressing rat TRPV1. The potentiation seems to be caused by phosphorylation of the serine residues of TRPV1 by PKC. These data indicate that PKC-dependent potentiation of TRPV1 activities under hypoxia and hyperglycemia might be involved in early diabetic neuropathy. Mechanisms for the detection of alkaline pH by sensory neurons are not well understood, although it is well accepted that acidic pH monitoring can be attributed to several ion channels, including TRPV1 and ASICs. We found that alkaline pH activates TRPA1 and that the TRPA1 activation is involved in nociception, using Ca2+-imaging and patch-clamp methods. In addition, intracellular alkalization activated TRPA1 at the whole-cell level, and single-channel openings were observed in the inside-out configuration. Furthermore, intraplantar injection of ammonium chloride into the mouse hind paw caused pain-related behaviors, which were not observed in TRPA1-deficient mice. These results suggest that alkaline pH causes pain sensation through activation of TRPA1.
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西田 基宏, 渡辺 健太, 仲矢 道雄, 黒瀬 等2010 年 130 巻 3 号 p. 295-302
発行日: 2010/03/01
公開日: 2010/03/01
ジャーナル フリーActivation of Ca2+ signaling in cardiomyocytes induced by receptor stimulation or mechanical stress has been implicated in the development of cardiac hypertrophy. However, it is still unclear how intracellular Ca2+ targets specifically decode the alteration of intracellular Ca2+ concentration ([Ca2+]i) on the background of the rhythmic Ca2+ increases required for muscle contraction. In excitable cardiomyocytes, changes in the frequency or amplitude of Ca2+ transients evoked by Ca2+ influx-induced Ca2+ release have been suggested to encode signals for induction of hypertrophy, and a partial depolarization of plasma membrane by receptor stimulation will increase the frequency of Ca2+ oscillations. We found that activation of diacylglycerol (DAG)-responsive canonical transient receptor potential (TRPC) subfamily channels (TRPC3 and TRPC6) mediate membrane depolarization induced by Gq protein-coupled receptor stimulation. DAG-mediated membrane depolarization through activation of TRPC3/TRPC6 channels increases the frequency of Ca2+ spikes, leading to activation of calcineurin-dependent signaling pathways. Inhibition of either TRPC3 or TRPC6 completely suppressed agonist-induced hypertrophic responses, suggesting that TRPC3 and TRPC6 form heterotetramer channels. Furthermore, we found that hypertrophic agonists increase the expression of TRPC6 proteins through activation of G12 family proteins, leading to amplification of DAG-mediated hypertrophic signaling in cardiomyocytes. As heart failure proceeds through cardiac hypertrophy, TRPC3/TRPC6 channels may be a new therapeutic target for heart failure.
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清中 茂樹, 加藤 賢太, 西田 基宏, 森 泰生2010 年 130 巻 3 号 p. 303-311
発行日: 2010/03/01
公開日: 2010/03/01
ジャーナル フリーCa2+ signals control diverse cellular processes, ranging from ubiquitous activities like gene expression to tissue specific responses such as lymphocyte activation and cardiac diseases. TRPC channels control Ca2+ influxes that induce diverse cellular processes upon stimulation of plasma membrane receptors coupled to phospholipase C (PLC). Invention of subtype-specific inhibitors for TRPCs is crucial for distinction of respective TRPC channels that play particular physiological roles in native systems. Here, we identify a novel pyrazole compound (Pyr3) which selectively inhibits TRPC3 channels. Structure-function relationship studies of pyrazole compounds showed that the trichloroacrylic amide group is important for the TRPC3 selectivity of Pyr3. Electrophysiological and photoaffinity labeling experiments reveal a direct action of Pyr3 on the TRPC3 protein. In B lymphocytes, Pyr3 eliminated the B cell receptor-induced Ca2+ oscillation regulated by TRPC3-mediated Ca2+ influx. In the cardiac system, Pyr3 attenuates activation of nuclear factor of activated T cells and hypertrophic growth in myocytes and pressure overload-induced hypertrophy in vivo. Thus, the TRPC3-selective inhibitor Pyr3 is useful for treatments of TRPC3-mediated diseases and for clarification of crucial and widespread functions of TRPC3 as well.
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山野 昭人2010 年 130 巻 3 号 p. 313-314
発行日: 2010/03/01
公開日: 2010/03/01
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田中 大輔2010 年 130 巻 3 号 p. 315-323
発行日: 2010/03/01
公開日: 2010/03/01
ジャーナル フリーFragment-Based Drug Discovery (FBDD) has been recognized as a newly emerging lead discovery methodology that involves biophysical fragment screening and chemistry-driven fragment-to-lead stages. Although fragments, defined as structurally simple and small compounds (typically <300 Da), have not been employed in conventional high-throughput screening (HTS), the recent significant progress in the biophysical screening methods enables fragment screening at a practical level. The intention of FBDD primarily turns our attention to weakly but specifically binding fragments (hit fragments) as the starting point of medicinal chemistry. Hit fragments are then promoted to more potent lead compounds through linking or merging with another hit fragment and/or attaching functional groups. Another positive aspect of FBDD is ligand efficiency. Ligand efficiency is a useful guide in screening hit selection and hit-to-lead phases to achieve lead-likeness. Owing to these features, a number of successful applications of FBDD to “undruggable targets” (where HTS and other lead identification methods failed to identify useful lead compounds) have been reported. As a result, FBDD is now expected to complement more conventional methodologies. This review, as an introduction of the following articles, will summarize the fundamental concepts of FBDD and will discuss its advantages over other conventional drug discovery approaches.
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半沢 宏之, 滝沢 剛2010 年 130 巻 3 号 p. 325-333
発行日: 2010/03/01
公開日: 2010/03/01
ジャーナル フリーNuclear magnetic resonance (NMR) is a versatile technique for the pharmaceutical industry. From organic chemistry to MRI, there are a number of applications of NMR. Among them, biomolecular NMR has been used for structure determination of biomolecules and analyzing the interaction between a target protein and its inhibitors. In the context of fragment-based drug discovery (FBDD), NMR has been known as a fragment screening technique, because NMR is good at detecting a weak binding compound in an accurate manner. Generally, the NMR technique for fragment screening is classified into two families: the ligand-based technique and the protein-based technique. The latter technique requires stable isotope labeled protein and also can be applied to a relatively small MW protein target. In the ligand-based technique such as saturation transfer difference (STD) and WaterLOGSY, only the NMR signals of the ligands are observed. The disadvantage of STD and WaterLOGSY is that the non-specific binding is also observed and a competition experiment is required in order to select the specific binding compound. Due to the difference in the consumption of the protein sample, the ligand-based technique has generally been used recently as a primary screening.
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山野 昭人2010 年 130 巻 3 号 p. 335-340
発行日: 2010/03/01
公開日: 2010/03/01
ジャーナル フリーThe first step of FBDD is fragment-based screening (FBS). There are various analytical methods used to perform FBS: NMR, X-rays, SPR, etc. The advantage of X-ray structure analysis in FBS is that it can cope with relatively large structural changes upon the binding of a fragment and unexpected events such as multiple binding. The first thing needed to perform FBS by X-rays is a fragment library. The library currently employed at our laboratory was designed especially for X-ray structure analysis and consists of 384 compounds. This library was built based on Ro3 and special attention was given to eliminating ambiguity when interpreting electron density. FBS by X-rays requires more than 100 times more data collection and structure analysis. Recent development of critical technologies dramatically reduced the time required for X-ray structure analysis. Additionally, development of software and the incorporation of an industrial robot to a laboratory system has enabled us to construct a fully automated structure analysis system. However, there still are some limitations to X-ray structure analysis. It demands hundreds of high quality crystals and those crystals must not only survive soaking of compounds dissolved in DMSO but also be resistant to X-ray damage. In this article, a practical example of FBS by X-rays will be presented using HSP90 along with facts on the limitations of X-rays.
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三浦 隆昭2010 年 130 巻 3 号 p. 341-348
発行日: 2010/03/01
公開日: 2010/03/01
ジャーナル フリーA surface plasmon resonance (SPR) optical biosensor is a label-free biophysical device which can detect molecular interaction in real time. SPR is an emerging technology for fragment screening, the first step in fragment-based drug discovery. Low levels of protein consumption and the ability to detect interactions with Kd as low as mM make this technology particularly attractive. Inherently small SPR responses due to fragment binding had been an issue but, owing to well-established experimental protocols, such responses have become readily detectable. Medium-throughput instruments are now on the market from several manufacturers that enable complete screening of a library with several thousand compounds within a few days. In fragment screening, test compounds are injected at a high concentration because of the low affinity expected for small molecules, making it likely that many false positives arise from non-specific binding to an unrelated part of the target protein. Such false positives have to be eliminated by a well-designed assay cascade so as to select true hits which can then be subjected to X-ray crystallization to obtain detailed structural information. SPR-based direct binding assays have to be developed with a sufficient binding capacity and good reproducibility with a Z′-factor larger than 0.6. In selecting hit candidates from fragment primary screens, the shape of sensorgrams, binding stoichiometry and response level to reference proteins when available must be carefully evaluated. The selected compounds from primary screening need to be further examined in terms of dose-dependence and binding competition against tight binding reference compounds to ensure that they bind to the designated site of the target protein.
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高橋 理, 増田 吉昭, 室谷 歩, 古谷 利夫2010 年 130 巻 3 号 p. 349-354
発行日: 2010/03/01
公開日: 2010/03/01
ジャーナル フリーAn important step to promote fragment-based drug design (FBDD) is to find high-quality fragment molecules. Therefore the design of the fragment library is the most crucial stage. In our fragment library, the main considerations are ligand efficiency (LE), diversity, and solubility with drug-like properties. We especially considered LE to raise hit probability in screening. We estimated LE of the fragment molecule based on known LE values of the active compounds. We also developed a docking program suitable for screening fragments rather than drug compounds. Furthermore, we explored fragment-linking program, which links together fragments that bind to adjacent sites on a target protein so as to promote FBDD in silico.
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総説
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川島 悦子, 釜池 和大2010 年 130 巻 3 号 p. 355-375
発行日: 2010/03/01
公開日: 2010/03/01
ジャーナル フリーOn the basis of reports that a minor groove binder pyrrolepolyamide can interfere with gene expression by the sequence-specific recognition of DNA, we expected that nucleoside bearing a pyrrolepolyamide would be able to regulate gene expression. Therefore, we designed and synthesized the pyrrolepolyamide-adenosine (Hybrid 1) and -2′-deoxyguanosine hybrids (Hybrid 2 and Hybrid 3) as lead compounds for gene expression control compounds. The pyrrolepolyamide frame of Hybrid 2 and Hybrid 3 combines at the 2-exocyclic amino group of the 2′-deoxyguanosine by a linker and the 2-exocyclic amino group of guanine exists in the minor groove side of the duplex. Hybrid 2 is the 2′-deoxyguanosine-pyrrolepolyamide hybrid using the 3-aminopropionyl linker, while Hybrid 3 uses the 3-aminopropyl linker. An evaluation of the DNA binding sequence selectivity was performed by analysis of Tm values and CD spectra, using distamycin A as a contrast. Hybrid 3 has provided more excellent sequence-distinguishable ability than other hybrids and Distamycin A. Moreover, on the basis of these results, we synthesized oligonucleotides conjugated to Hybrid 4, which is stable under conditions of DNA oligonucleotide solid phase synthesis, arranged from Hybrid 3. From Tm values and CD spectral analysis, it was found that oligonucleotides conjugating Hybrid 4 possess high recognition ability and very high binding ability for the DNA that includes the pyrrolepolyamide binding sequence.
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岡 孝己, 大谷 政博, 鈴木 順一朗2010 年 130 巻 3 号 p. 377-388
発行日: 2010/03/01
公開日: 2010/03/01
ジャーナル フリーIn order to find novel bioactive molecules regulating differentiation and hormone secretion of pancreatic endocrine cells, the effects of various substances including purinergic receptor agonists and inhibitors of polyamine biosynthesis were examined in pancreatic islets and several pancreatic cell lines. The nicotinic alpha3beta4 receptor was found to be present and capable of increasing cytoplasmic Ca2+ concentration ([Ca2+]i) and insulin secretion in mouse pancreatic Beta-TC6 cells. Activation of both nicotinic and muscarinic M3/M4 receptors resulted in reduction of insulin release when compared with stimulation of muscarinic receptor alone in Beta-TC6 cells. In mouse islets, purinergic P2Y1 and P2Y6 receptors, which are coupled to Gq proteins, were expressed and appeared to regulate insulin secretion through Ca2+ mobilization from intracellular stores. Similar results were observed in Beta-TC6 cells. Spermidine, one of polyamines, was found to modulate insulin synthesis and [Ca2+]i in Beta-TC6 cells by use of a specific spermidine synthesis inhibitor, trans-4-methylcyclohexylamine (MCHA). Antizyme, which binds to ornithine decarboxylase (ODC) and thereby reduces the cellular polyamine level, was found to be necessary for conversion of ASPC-1 cells, a pancreatic ductal tumor cell line, into alpha-cells forming the islet-like structure and expressing glucagon gene. These findings help advance our understanding of the complex mechanisms involved in the regulation of pancreatic endocrine cell function and develop new therapeutic agents in diabetes mellitus.
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一般論文
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上村 直樹, 塩川 貴子, 與儀 愛梨, 赤澤 真, 島崎 紀子, 太田 隆文2010 年 130 巻 3 号 p. 389-396
発行日: 2010/03/01
公開日: 2010/03/01
ジャーナル フリーTo survey the difference in appearance between multiple-specification press-through-package (PTP) drug products and to attempt to evaluate their effectiveness as discriminating factors based on dispensing incidents. Front and back sides of, respectively, 153 and 134 PTP drug products of multiple specifications stockpiled in the author's pharmacy were surveyed for differences in wording and appearance between specifications of the same type of drug. Fifty six dispensing incidents with 40 sets occurred over a year and they were analyzed for the appearance similarity of the front side. The difference factors detected in the 40 sets of “mix-ups” were also reviewed after similarity-omitted counting. We identified six factors with difference in appearance: color-related (letter front or patterns, sheet, medicine) and shape- or pattern-related details (sheet and medicine sizes, patterns). Multiple differences on the front packaging of the same type of drug were identified in 93% of the sets, while only one difference was found in about half of the sets on the back, indicating that pharmaceutical companies placed more emphasis on the front side to discriminate their features. When reviewed by similarity-omitted counting, the ratio of sets with only one difference in the 40 mix-ups was higher than those to 128 sets of non-mix-ups, the total sets except the mix-ups, while the ratio of sets with two differences was lower. In addition, the ratio of sets in which only color-related factors differed in the 40 mix-ups was higher than that in the corresponding category to the 128 sets of non-mix-ups. Various discriminating factors were used in combination on the front side of multiple-specification PTP drug products. A combined use of shape- or pattern-related and color-related factors probably reduces dispensing incidents among products with multiple specifications. However, further accumulation of incident data and multifactor analysis of those data seem necessary to clarify the function of difference in appearance in dispensing incidents
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Hardevinder Pal SINGH, Ashok Kumar TIWARY, Subheet JAIN原稿種別: Regular Article
2010 年 130 巻 3 号 p. 397-407
発行日: 2010/03/01
公開日: 2010/03/01
ジャーナル フリーIn the present study, an attempt was made to develop a cyclodextrin-colchicine complex and to study its effect on skin permeation and deposition of colchicine. Colchicine β cyclodextrin (BCD) complex was prepared by freeze-drying method and complex formation was confirmed by NMR and in vitro drug release study. Formulation containing cyclodextrin-drug complex showed 6-fold increase in transdermal flux in comparison with drug solution. Skin retention studies were carried out with the objective of determining the depot effect of elastic liposomes in skin. The amount of drug deposited was 12.4-fold higher in case of elastic liposomes of colchicine-cyclodextrin complex (567±1.5 μg) than drug solution (46±1.1 μg). The biological evaluation of various vesicular formulations and drug solution was carried out using monosodium urate-induced air pouch model. The results of anti-gout activity in rats showed better and sustained biological effects over 24 h measured in terms of exudate volume, reduction in leukocyte count, decrease in inflammatory cell accumulation, and collagen deposition with colchicine-BCD elastic liposomal formulation than drug solution. Hence the present study reveals that colchicine-cyclodextrin-elastic liposomes approach possesses good potential to enhance skin accumulation, prolong drug release, and improve the site-specificity of colchicine.
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Xuefan XU, Qingyu XIANG, Zhiyao HE, Yuehua LIU, Dan ZHOU, Xuan QIN, Ti ...原稿種別: Regular Article
2010 年 130 巻 3 号 p. 409-418
発行日: 2010/03/01
公開日: 2010/03/01
ジャーナル フリーThis paper reports both the optimization of aconitine entrapment and its release from biodegradable poly(d,l-lactide-coglycolide) (PLGA) nanoparticles prepared using the O/W single-emulsion/solvent-evaporation technique. The influence of several parameters, such as the initial aconitine mass, aqueous-phase pH, volume ratio of aqueous/organic phase (W/O), PLGA concentration in the organic phase, etc., on aconitine encapsulation were investigated. The optimized nanoparticles had an entrapment efficiency of 88.40±3.02% with drug loading capacity of 9.42±2.93%. Crystallization growth, which played a crucial role in hindering the incorporation of aconitine into the polymer carrier, was proposed. Differential scanning calorimetry and X-ray powder diffraction demonstrated that aconitine existed in an amorphous state or as a solid solution in the polymeric matrix. The in vitro release profiles exhibited a sustained release of aconitine from nanoparticles and a pH-dependent character in phosphate-buffered saline with different pH values. Moreover, aconitine-loaded PLGA nanoparticles could lead to improvement in the stability of aconitine. This work demonstrated the feasibility of encapsulating aconitine into PLGA nanoparticles using the O/W single-emulsion/solvent-evaporation technique.
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Rui CHEN, Yong QIAN, Rui LI, Qing ZHANG, Dongfei LIU, Miao WANG, Qunwe ...原稿種別: Regular Article
2010 年 130 巻 3 号 p. 419-424
発行日: 2010/03/01
公開日: 2010/03/01
ジャーナル フリーA new system for the local delivery of methazolamide to the eye has been developed based on calcium phosphate (CaP) nanoparticles. The methazolamide loaded CaP nanoparticles were prepared through the formation of an inorganic core of CaP and further adsorption of the methazolamide. The maximum loading of methazolamide studied using UV-vis spectrophotometry was about 0.2% (w/w). The drug-loaded particles had a negative surface charge at about -30 mV while their mean particle diameter was estimated to be 256.4 nm. In vitro release studies demonstrated diffusion-controlled release of methazolamide from the CaP nanoparticles over a period of 4 h. In vivo studies indicated that the intraocular pressure (IOP)-lowering effect of the inorganic nanoparticle eye drops lasted for 18 h, which was significantly better than the effect of 1% brinzolamide eye drops (6 h). Physical stability studies indicated that the preparation was stable for 6 months at 40°C. These findings suggested that methazolamide bound to CaP nanoparticles might be useful in the local treatment of glaucoma.
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Yuebin GE原稿種別: Regular Article
2010 年 130 巻 3 号 p. 425-430
発行日: 2010/03/01
公開日: 2010/03/01
ジャーナル フリーThe rapid-release mechanisms of standard extract from Ginkgo biloba leaf (EGb) in the polyethylene glycol (PEG) 6000 dispersions were investigated. The apparent equilibrium solubilities of the total flavone glycosides and the soluble solid materials of EGb increased linearly with the increasing concentrations of PEG 6000 solutions. In DSC curves, the peak, onset and endset temperatures of solid dispersions decreased with the increase of EGb weight percent. At the high drug loading, the initial dissolution rates of the total flavone glycosides of EGb had no significant change while the rates of PEG 6000 reduced with the drug concentration increase. The rates of PEG 6000 had no significant change as well as the rates of drug increased with the drug concentration increase at the low drug loading. The results indicated that there were apparent evidences for eutectic observation and soluble complex formation in the two-component solid dispersion of EGb and PEG 6000. The dispersions may belong to drug-controlled dissolution model at high drug loadings and carrier-controlled dissolution model at low drug loadings.
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松本 圭司, 内藤 隆文, 堀 雄史, 鈴木 直哉, 宮本 康敬, 髙科 嘉章, 大西 一功, 川上 純一2010 年 130 巻 3 号 p. 431-439
発行日: 2010/03/01
公開日: 2010/03/01
ジャーナル フリーAn academic subcommittee of Japanese Society of Hospital Pharmacists formulated the guideline for the sterile preparation of antineoplastic agents in 2008. The practical methods to monitor a workplace contamination and occupational exposure to antineoplastic agents have not been introduced into a hospital setting yet. The aims of this study were to develop a monitoring method using doxorubicin for workplace contamination and occupational exposure to antineoplastic agents and to apply it to surveillance in a hospital setting. The surface contamination of workplace was wiped with non-woven fabric containing 70% 2-propanol. The occupational exposure was evaluated by spot urine sampling during 24 hours. Chromatographic separation was achieved by a reverse phase HPLC. Doxorubicin and fluorescein (internal standard) were detected at an excitation and emission wavelength of 470 and 550 nm, respectively. The monitoring method was applied to survey the workplace contamination and occupational exposure to antineoplastic agents in Hamamatsu University Hospital. The calibration curves for doxorubicin were linear over concentration ranges of 1.5-729 ng/100 cm2 for surface contamination and 1.0-486 ng/ml for the urine. The run time was 10 min. The intra- and interassay precisions were within 8.5%. As the surveillance in a hospital setting, the flow line adhering to the guideline kept the exposure to low level. In addition, the occupational exposure in the workers was not observed. In conclusion, this study developed the monitoring method using doxorubicin for the workplace contamination and occupational exposure to antineoplastic agents. This method can be utilized to survey in a hospital setting.
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ノート
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福本 恭子, 藤村 保夫, 楠本 正明, 多々見 良三, 上野 和行2010 年 130 巻 3 号 p. 441-446
発行日: 2010年
公開日: 2010/03/01
ジャーナル フリーThe graduate students in our laboratory underwent 4-5 months of training at Maizuru Kyosai Hospital. To evaluate the effectiveness of this long-term practical training course of the off-campus hospital, we conducted a questionnaire survey before and after the course among the students and the pharmacists. The results of the survey suggest that the students gained experience regarding pharmaceutical management and came to understand the importance of pharmaceutical care during the course. They had an opportunity to connect clinical practice with the research activities conducted at the university. With regard to the pharmacists, this course has motivated them to act as mentors during the practical training, and therefore was also of significance to them. However, this long-term practical training at the off-campus hospital necessitated a change in lifestyle and living arrangements for the students, which placed stress on them. They required emotional support from university staff before and during the placement. These results show that in order to maintain close collaboration with the hospital and to ensure the success of long-term practical training at an off-campus hospital, academic and emotional support for the students is necessary.
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磯部 孝彦, 長田 久美子2010 年 130 巻 3 号 p. 447-450
発行日: 2010/03/01
公開日: 2010/03/01
ジャーナル フリーWe investigated antibacterial activities of ten compounds from Isodon species against five strains of Escherichia coli, Staphylococcus epidermidis, Serratia marcescens, Streptococcus mutans, and Helicobacter pylori. The compounds with the MIC values of 25 μg/ml were isodocarpin against Sta. epidermidis, Str. mutans, and H. pylori, nodosin against Sta. epidermidis and Str. mutans, oridonin against Ser. marcescens, and pedalitin against H. pylori.
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菱沼 滋, 庄司 優原稿種別: Note
2010 年 130 巻 3 号 p. 451-455
発行日: 2010/03/01
公開日: 2010/03/01
ジャーナル フリーHistamine regulates a variety of physiological or pathophysiological processes via the activation of Gq/11 protein-coupled and Ca2+-mobilizing histamine H1 receptors, including smooth muscle contraction. We have found that histamine induces progression from heterologous to homologous desensitization of contraction under normal physiological conditions in smooth muscle of guinea pig taenia caeci. In this study, we characterized the development of histamine-induced desensitization under Ca2+-free conditions and we found that histamine developed only a homologous phase of desensitization to histamine with an increase in EC50 values for histamine and basal tone. In contrast, histamine treatment reduced EC50 values for a muscarinic agonist, carbachol, and depolarizing high K+. These results suggest that the failure of excess histamine to induce a normal Ca2+ response under Ca2+-free conditions may lead to homologous desensitization to histamine with apparent hyper-reactivity of smooth muscles to cholinergic and depolarizing stimuli. We estimate that this characteristic of histamine to change smooth muscle contractility may be potentially involved in its physiological and pathophysiological aspects, including histamine-induced allergic conditions, depending on cellular circumstances.
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資料
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杉山 育美, 工藤 賢三, 高橋 勝雄, 佐塚 泰之2010 年 130 巻 3 号 p. 457-461
発行日: 2010/03/01
公開日: 2010/03/01
ジャーナル フリーWe have studied AmBisome®, which is amphotericin B containing liposomes, used in the treatment of mycosis. Any potential problems regarding the liposome formulation remain unknown because it is a new dosage form. AmBisome® is useful in that it can decrease adverse reactions while maintaining a therapeutic effect. However, it is doubtful whether AmBisome® is suitable in a busy clinical environment. For example, this formulation should be filtered with an established filter. We then carried out a questionnaire survey involving medical staff (doctors and nurses) to clarify the problems regarding the liposome formulation and its practical utilization. Most doctors were satisfied with the effect of AmBisome®, but about 90% of nurses who had used the preparation answered that it was troublesome to use the filter. On the other hand, only 40% of doctors understood how to use the filter when AmBisome® was made up; 14% of nurses also did not know how to use the filter. We thought this was because they were not shown how to use it; actually, 30% of doctors were shown the preparation method by medical representatives (MR), although no nurse received an explanation. The residual rate of amphotericin B on 100 used filter pieces differed 50-fold between the minimum and maximum values. AmBisome® is effective as an antifungal agent. However, pharmaceutical companies must liaise with medical staff for its effective clinical use. We hope that such companies will have exchanges with medical staff to develop safe and simple medicines, and that liposomes will be effective for many patients.
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