YAKUGAKU ZASSHI
Online ISSN : 1347-5231
Print ISSN : 0031-6903
ISSN-L : 0031-6903
123 巻 , 7 号
選択された号の論文の13件中1~13を表示しています
総説
  • 水野 亘恭, 新熊 傳治, 濱口 常男
    2003 年 123 巻 7 号 p. 477-493
    発行日: 2003/07/01
    公開日: 2003/07/08
    ジャーナル フリー
    Phenytoin (pulverized powder), mefenamic acid (capsule), and sulpiride (film-coated tablet) are currently available on the Japanese market. For absorption of these drugs from their pharmaceutical preparations, they must disintegrate and dissolve during passage through the gastrointestinal tract. The bioavailability of these drugs differ among different pharmaceutical preparations and even for the same preparation. This led to a review of the influence of the features of pharmaceutical preparations and the physicochemical properties of film coating materials as well as the physiologic factors affecting drug bioavailability. The influence of coadministered drugs and concomitant intake of beverages and food on the bioavailability of drugs from pharmaceutical preparations is also described.
  • 砂野 哲, 関口 富美子
    2003 年 123 巻 7 号 p. 495-515
    発行日: 2003/07/01
    公開日: 2003/07/08
    ジャーナル フリー
    Endothelium–dependent relaxation (EDR) in the blood vessels of spontaneously hypertensive rats (SHR) and the role of nitric oxide (NO) in the initiation of hypertension are reviewed. EDR was impaired in blood vessels of SHR depending on age and degree of hypertension when compared with those of normotensive rats. The cause of the impairment varied among the type of blood vessels: a decrease in the production of NO and endothelium–derived relaxing factor (EDRF) and an increase in the production of endothelium–derived contracting factor (EDCF) are the main causes of the impairment in large arteries, while a decrease in endothelium–dependent hyperpolarization and increased release of EDCF are the main causes of the impairment in small arteries. Interactions among these endothelium–derived factors and changes in the interactions are also causes of impairment. Superoxide may be involved in the impairment of EDR by destroying NO. The endothelium depresses smooth muscle contraction, including spontaneous tone developed in vascular smooth muscle, and the depressing effect of the endothelium is impaired in the preparations from SHR. The endothelium of blood vessels of SHR are structurally injured as demonstrated by scanning electron microscopy. Antihypertensive treatment prevented these functional and structural changes. Chronic treatment with inhibitors of NO production in normotensive rats impaired EDR and elevated blood pressure. The impairment of EDR is a secondary change due to continued hypertension, and early initiation of antihypertensive therapy is recommended.
  • 八木  晟, 竹尾  聡
    原稿種別: その他
    専門分野: その他
    2003 年 123 巻 7 号 p. 517-532
    発行日: 2003年
    公開日: 2003/07/08
    ジャーナル フリー

    Cinnamoyl, p-coumaroyl, feruloyl, caffeoyl aloesin, and related compounds were isolated from Aloe species. The antiinflammatory and antioxidative activities of these compounds were examined based on the structure-activity relationship. It was suggested that the bioactivities may link to acyl ester groups in sin, together with those of aloesin-related compounds. However, investigations using the contact hypersensitivity response indicated a preventive effect of aloesin on the UV-B-induced immune suppression. Furthermore, aloesin inhibited tyrosine hydroxylase and dihydroxyphenylalanine (DOPA) oxidase activities of tyrosinase from normal human melanocyte cell lysates. These results show that aloesin prevents not only UV-B-induced immune suppression, but also could be a positive pigment-altering agent for cosmetic application. In preclinical study, aloe extract was investigated using phagocytosis and nitroblue tetrazolium chloride (NBT) reduction in adult bronchial asthma, and high molecular-weight materials, such as polysaccharide and glycoprotein fractions, were identified as active ingredients. The neutral polysaccharides, aloemannan and acemannan showed antitumor, antiinflammatory and immunosuppressive activities, and glycoprotein fractions with bradykinindegrading and cell proliferation-stimulating activities were identified from the nondialysate fraction of the gel part of Aloe species. Verectin fractionated from Aloe vera gel was examined biochemically and immunochemically, and verectin antibody was used in the appraisal of commercial Aloe vera gel products. It was reported that aloesin stimulates the proliferation of cultured human hepatoma SK-Hep 1 cells. Thus aloesin, related compounds, and high molecular-weight materials, such as aloemannan and verectin, may act in concert to exert therapeutic properties for wounds, burns and inflammation. The biodisposition of fluoresceinylisothiocyanate (FITC)-labeled aloemannan (FITC-AM) with the homogenate from some organs in mice was demonstrated, and FITC-AM was metabolized to a smaller molecule (MW 3000) by the large intestinal microflora in feces. The modified aloe polysaccharide (MW: 80000) with cellulase under restricted conditions, immunologically stimulated the recovery of UV-B-induced tissue in jury. Thus the modified polysaccharides of aloemannan, together with acemannan (MW: about 600000), are expected to participate in biological activity following oral administration. The effects of tanshinone VI, a diterpenoid isolated from Salvia miltiorrhiza, on the heart are reviewed. First, the effects on the posthypoxic recovery of contractile function of perfused rat hearts were examined. Hypoxia/reoxygenation induced a release of purine nucleosides and bases (ATP metabolites) and resulted in little recovery of contractile force of reoxygenated hearts. Pretreatment of the perfused heart with 42n tanshinone VI under hypoxic conditions attenuated the release of ATP metabolites during hypoxia/reoxygenation. Treatment with tanshinone VI enhanced the posthypoxic recovery of myocardial contractility. These results show that tanshinone VI may protect the heart against hypoxia/reoxygenation injury and improve the posthypoxic cardiac function. Second, the effects of tanshinone VI on in vitro myocardial remodeling were examined. Cardiomyocytes and cardiac fibroblasts were isolated from neonatal rat hearts, and simultaneously prepared insulin-like growth factor-1 (IGF-1) induced the hypertrophy of cardiomyocytes. IGF-1 increased the collagen synthesis of cardiac fibroblasts, that is, in vitro fibrosis. The hypertrophy of cardiomyocytes was attenuated in the presence of tanshinone VI in the culture medium. The fibrosis of cardiac fibroblasts was decreased by treatment with tanshinone VI. When tanshinone VI was added to cardiac fibroblast-conditioned medium, the medium-mediated hypertrophy of cardiomyocytes was also attenuated....

  • 黒田 良太郎, 川畑 篤史
    2003 年 123 巻 7 号 p. 533-546
    発行日: 2003/07/01
    公開日: 2003/07/08
    ジャーナル フリー
    A recent PET study revealed that the first and second somatosensory cortices (SI, SII), and the anterior cingulate cortex are activated by painful peripheral stimulation in humans. It has become clear that painful signals (nociceptive information) evoked at the periphery are transmitted via various circuits to the multiple cerebral cortices where pain signals are processed and perceived. Human or clinical pain is not merely a modality of somatic sensation, but associated with the affect that accompanies sensation. Consequently, pain has a somatosensory–discriminative aspect and an affective–cognitive aspect that are processed in different but correlated brain structures in the ascending circuits. Considering the physiologic characteristics and fiber connections, the SI and SII cortices appear to be involved in somatosensory–discriminative pain, and the anterior cingulate cortex (area 24) in the affective–cognitive aspect of pain. This paper deals with the ascending pain pathways from the periphery to these cortices and their interconnections. Our recent findings on the protease–activated receptors 1 and 2 (PAR–1, and –2), which are confirmed to exist in the dorsal root ganglion cells, are also described. Activation of PAR–2 during inflammation or tissue injury at the periphery is pronociceptive, while PAR–1 appears to be antinociceptive. Based on these findings, PAR–1 and PAR–2 are attracting interest as target molecules for new drug development.
  • 田中 智之
    2003 年 123 巻 7 号 p. 547-559
    発行日: 2003/07/01
    公開日: 2003/07/08
    ジャーナル フリー
    Histamine is involved in a variety of physiologic responses, such as inflammation, type I allergy, gastric acid secretion, and neurotransmission. Previous studies have focused on specific receptors for histamine and histamine release through degranulation, and the regulation of histamine synthesis and its physiologic roles remain to be clarified. We have studied histidine decarboxylase (HDC), the rate-limiting enzyme for mammalian histamine synthesis. Immunocytochemical approaches with an anti-HDC antibody revealed that histamine synthesis occurs in two distinct compartments of mast cells, cytosol and granules, and is regulated by the posttranslational processing of HDC. We also found that histamine synthesis in mast cells is markedly induced by IgE even in the absence of antigens, which may be relevant to enhanced responses of mast cells under allergic conditions. We then developed HDC-deficient mice by gene targeting to investigate the physiologic roles of histamine. We not only confirmed that histamine is essential for type I allergy and stimulates gastric acid secretion, but also found that histamine may regulate the proliferation and differentiation of mast cells. Furthermore, in HDC-deficient mice histamine produced by infiltrated neutrophils can suppress the production of antitumoral cytokines, such as interferon-γ and tumor necrosis factor-α through H2 receptors in the tumor tissues. In this review, we describe recent topics in histamine research, including our results focusing on histamine synthesis and its physiologic roles.
  • 渡部 俊彦
    2003 年 123 巻 7 号 p. 561-567
    発行日: 2003/07/01
    公開日: 2003/07/08
    ジャーナル フリー
    Hyphal cells of Candida albicans bind to human hemoglobin, but not yeast cells. The amount of hemoglobin receptor is significantly higher in hyphal cells than on yeast cells. Only the hyphal cells of C. albicans use hemoglobin as a source of iron. The culture supernatant of C. albicans promoted the disruption of human red blood cells (RBC). Hemolytic activity was detected in a sugar-rich fraction (about 200kDa) purified by Sephacryl S-100 chromatography. As the hemolytic activity was adsorbed by concanavalin A (Con A)-Sepharose, the hemolytic factor might be a mannoprotein. The activity was inactivated by periodate oxidation, indicating that the sugar moiety of the mannoprotein plays an important role in hemolysis. The structure of the sugar moiety of the mannoprotein was identified as a cell wall mannan by 1H-NMR analysis, and purified C. albicans mannan promoted the disruption of RBC. The binding of mannan to RBC was demonstrated by flow cytometric analysis and was inhibited by the addition of the band 3 protein inhibitor, 4,4′-diisothiocyanato-stilbene-2,2′-disulfonic acid (DIDS). The hemolysis caused by mannan is inhibited by DIDS, 4-acetamido-4′-isothiocyanato-stilbene-2,2′-disulfonic acid, and Bis (sulfosuccinimidyl) suberate, but not by pyridoxal-5′-phosphate. A new platinum derivative of the form H[Pt(IV) (Hdigly)Cl2(OH)2] (Hdigly=glycylglycine) has candidacidal activity 10-fold lower than that of cisplatin.
  • 宮田 昌明
    2003 年 123 巻 7 号 p. 569-576
    発行日: 2003/07/01
    公開日: 2003/07/08
    ジャーナル フリー
    Several gene knockout mice have been widely used to analyze the role of drug-metabolizing enzymes in pharmacologic and physiologic responses. The metabolic shift of endogenous and exogenous compounds causes pharmacologic and physiologic alterations. Microsomal epoxide hydrolase (mEH)-null mice are less susceptible to the skin tumorigenesis, splenic immunotoxicity, and embryonic toxicity of 7,12-dimethylbenz[a]anthracene (DMBA). The production of DMBA-3,4-diol is detected in the target organs of wild-type mice, but not in those of mEH-null mice. Soluble epoxide hydrolase (sEH)-null mice exhibit markedly reduced rates of epoxyeicosatrienoic acid conversion to dihydroxyeicosatrienoic acid in the liver and kidney. Furthermore, sEH-null male mice have a lower blood pressure phenotype compared with male wild-type mice, suggesting the importance of sEH in blood pressure regulation. Nuclear bile acid receptor, farnesoid X receptor (FXR)-null mice are distinguished from wild-type mice by elevated bile acid levels in the liver and serum. However, hepatic lithocholic acid (LCA) levels are lower in LCA-fed FXR-null female mice compared to those in wild-type female mice. Furthermore, FXR-null female mice are less susceptible to liver damage by LCA compared with female wild-type mice. Marked increases in hepatic LCA-sulfating activity and hepatic hydroxysteroid sulfotransferase and biliary sulfated bile acid levels are detected in FXR-null female mice, suggesting the protective role of hydroxysteroid sulfotransferase in LCA-induced liver damage. These and other studies indicate that mice null for drug-metabolizing enzymes and nuclear receptors are of great value in the study of the role of drug-metabolizing enzymes in pharmacologic and physiologic responses.
  • 安池 修之
    2003 年 123 巻 7 号 p. 577-585
    発行日: 2003/07/01
    公開日: 2003/07/08
    ジャーナル フリー
    The chemistry of chiral ligands for transition metal-catalyzed asymmetric reactions is an interesting research field in synthetic chemistry and has recently been the focus of much attention. Although a number of chiral ligands containing phosphorus (P) and arsenic (As) have been widely studied and are well documented, asymmetric reactions with optically active organoantimony compounds have not been reported so far. We are interested in the synthesis and utilization of optically active organoantimony compounds for asymmetric synthesis. We present here the synthesis and resolution of Sb-chiral and C2-symmetric compounds containing antimony as well as their physical and chemical properties. Resolution of (±)-1-phenyl-2-trimetylsilylstibindole (1), Sb(R/S)-(aryl) [2-(S)-(1-dimethylaminoethyl) phenyl] (p-tolyl)stibane (9), and (±)-2,2′-bis(diarylstibano)-1,1′-binaphthyl (13) can be achieved by the separation of a mixture of the diastereomeric antimony-palladium complexes. The optically pure Sb-chiral stibanes (1, 9) isolated here were optically stable, and no racemization on the chiral antimony center was observed even when they were heated under a neutral or a basic condition. Single-crystal X-ray analysis of Sb-chiral triarylstibane 9b-B revealed the presence of an intramolecular interaction between the antimony and nitrogen atoms. The optically active BINASb (13) can be used as powerful chiral ligand for the palladium-catalyzed asymmetric allylic alkylation of racemic 1,3-diphenyl-2-propen-1-yl acetate with dimethyl malonate. We also report the synthesis, molecular structure, and fluxional behavior of the (R)-(−)-7-p-tolyldinaphtho [2, 1-b; 1′,2′-d]stibole (21c) which is the first isolated example of optically active C2-symmetric group 15 dinaphthoheteroles.
一般論文
  • 西村  誠, 岩永 武敏, 大軽 靖彦, 高木 敦子, 池田 康行
    2003 年 123 巻 7 号 p. 587-591
    発行日: 2003/07/01
    公開日: 2003/07/08
    ジャーナル フリー
    The present study describes how to process human postheparin plasma (PHP) containing hepatic triglyceride lipase (HTGL) that is utilized as a standard material of HTGL for the quantification of HTGL mass in human plasma. The optimal storage conditions for PHP were established by monitoring the stability of HTGL molecules in PHP as an antigen, which was stored in the liquid, frozen, or lyophilized state, using purified human PHP-HTGL as the standard material and a commercial HTGL ELISA MARUPI kit, which is a direct sandwich enzyme-linked immunosorbent assay (ELISA). The HTGL ELISA MARUPI kit, for which the validity was confirmed by precision and dilution tests, showed that the immunoreactive mass of HTGL in lyophilized PHP remained stable for at least 12 months at a storage temperature of 4°C or lower. These results indicate that lyophilized PHP stored at a temperature of less than 4°C can be utilized as the standard material for the quantification of HTGL in human plasma using the HTGL ELISA MARUPI kit.
  • 桜井 信子, 飯塚  徹, 中山 繁樹, 船山 浩子, 野口 万里子, 永井 正博
    原稿種別: その他
    専門分野: その他
    2003 年 123 巻 7 号 p. 593-598
    発行日: 2003年
    公開日: 2003/07/08
    ジャーナル フリー
    The vasorelaxant activities of chicoric acid (Compound 1) from Cichorium intybus and dicaffeoyl-meso-tartaric acid (Compound 2) from Equisetum arvense L. in isolated rat aorta strips were studied. Compound 1 is a diester composed of (S,S)-tartaric acid and caffeic acid, and 2 is composed of its meso type. Both 1 and 2 showed slow relaxation activity against norepinephrine (NE)-induced contraction of rat aorta with/without endothelium. These compounds did not affect contraction induced by a high concentration of potassium (60 mM K+), while they inhibited NE-induced vasocontraction in the presence of nicardipine. These results show that the inhibition by 1 and 2 of NE-induced vasocontraction is due to a decrease in calcium influx from the extracellular space caused by NE. In addition, dicaffeoyl tartaric acids showed vasorelaxant activity, regardless of their stereochemistry.
  • 細山 広和, 杉本 明夫, 鈴木 裕子, 坂根  巌, 角田 隆巳
    2003 年 123 巻 7 号 p. 599-605
    発行日: 2003/07/01
    公開日: 2003/07/08
    ジャーナル フリー
    Banaba [Lagerstroemia speciosa (L.) Pers.] has been used as a folk medicine for diabetes in the Philippines. Using bioassay-guided separation, valoneaic acid dilactone (1) was isolated from the leaves as a potent α-amylase inhibitor. A simple and efficient method for the quantitative determination of valoneaic acid and its derivatives in Banaba extract was established. Valoneaic acid exists as the structural part of the polyphenols, which like flosin A, reginin A, and lagerstroemin, are characteristic constituents of Banaba. These derivatives were hydrolyzed to valoneaic acid by HCl and extracted with 2-butanone. This extract was subjected to HPLC analysis, and the contents of valoneaic acid determined as the whole valoneaic acid contents. Using this method, the whole valoneaic acid contents were measured in eight Banaba leaf decoctions. The α-amylase-inhibiting activities of the decoctions were dependent on the whole valoneaic acid contents. In addition, a strong linear correlation was observed between the whole valoneaic acid contents and total polyphenol contents. This analytical procedure is applicable to the chemical evaluation of Banaba.
ノート
  • Hiroyoshi MORIYAMA, Tohru IIZUKA, Masahiro NAGAI, Hideki MIYATAKA, Tos ...
    原稿種別: Note
    2003 年 123 巻 7 号 p. 607-611
    発行日: 2003/07/01
    公開日: 2003/07/08
    ジャーナル フリー
    Antiinflammatory activities of heat-treated Cassia alata leaf extract and kaempferol 3-O-gentiobioside(K3G) isolated from C. alata as an abundant flavonoid glycoside were studied by comparing their activities with the activities of sun-dried C. alata leaf extract. We observed strong inhibitory effects on Concanavalin A-induced histamine release from rat peritoneal exudate cells both in the extracts of heat-treated and sun-dried C. alata leaves. Furthermore, the heat-treated leaf extract exhibited stronger inhibitory effects than the effects of the sun-dried leaf extract at low concentrations in the studies of Concanavalin A-induced histamine release, 5-lipoxygenase inhibition, and also inhibition of cyclooxygenases (COX-1 and COX-2), whereas K3G showed weak inhibitory effects on Concanavalin A-induced histamine release, 5-lipoxygenase, and COX-1. No anti-hyaluronidase effect was detected in any of the materials tested.
資料
  • 伊勢 雄也, 室田 陽右, 高山 幸三, 成田  年, 鈴木  勉, 宋  静香, 片山 志郎, 平野 公晟
    2003 年 123 巻 7 号 p. 613-618
    発行日: 2003/07/01
    公開日: 2003/07/08
    ジャーナル フリー
    Recently, adverse reaction of non-steroidal anti-inflammatory drugs (NSAIDs) is the critical problem, although NSAIDs are one of the most commonly used classes of medications worldwide. Therefore, it is worthwhile to investigate the prescription frequency and the factors on adverse reactions of NSAIDs for post-operative pain in orthopedic patients of our hospital. In orthopedic field, loxoprofen was most prescribed in various kinds of NSAIDs. Logistic regression analysis strongly indicated that previous adverse reaction or allergy caused by drugs (not NSAIDs) or food is the important role in the adverse reaction of NSAIDs. In addition, significant correlation was observed between previous illness of gastrointestinal ulcer and gastrointestinal complication of NSAIDs. Moreover, the present study point out that pharmacist clinical intervention against the adverse reaction of NSAIDs may be saved on medical costs. Although further investigation may be needed, these present studies provide the good information for our medication management and instruction tasks (i.e. pharmaceutical care and counseling for inpatients) for post-operative pain of orthopedic patients.
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