Biological and Pharmaceutical Bulletin
Online ISSN : 1347-5215
Print ISSN : 0918-6158
ISSN-L : 0918-6158
24 巻 , 12 号
選択された号の論文の27件中1~27を表示しています
Biochemistry/Molecular Biology
Regular Articles
  • Shinya ABE, Susumu HASEGAWA, Moriyasu NIRASAWA, Masato SASAKI, Yasuhit ...
    2001 年 24 巻 12 号 p. 1343-1346
    発行日: 2001年
    公開日: 2002/06/28
    ジャーナル フリー
    Ever since the first observation of 67Ga accumulation in tumors and inflammatory lesions, 67Ga has been used to detect various tumors and inflammations. The aims of this study were to clarify whether or not transferrin is involved in the uptake of 67Ga by the regenerating liver after partial hepatectomy. The uptake of 67Ga by the liver of rats reached a maximum 2d after partial hepatectomy. In order to inhibit the binding of 67Ga to transferrin in the blood, FeCl3 was administered 5 min before the injection of 67Ga. The administration of FeCl3 decreased the uptake of 67Ga by the liver of the partially hepatectomized rats, suggesting that transferrin is involved in the uptake by the liver. However, 67Ga was taken up only slightly by hepatocytes obtained from the liver of these rats. We conclude that transferrin is involved in the uptake of 67Ga by the liver tissue of partially hepatectomized rats but is not involved in its entry into the hepatocytes. Only a slight amount of gallium-67 enters the hepatocytes, and may accumulate primarily in the extracellular matrix of the liver tissue of these rats.
  • Akihiro MICHIHARA, Makoto SAWAMURA, Yukio YAMORI, Kenji AKASAKI, Hiros ...
    2001 年 24 巻 12 号 p. 1347-1350
    発行日: 2001年
    公開日: 2002/06/28
    ジャーナル フリー
    We previously reported that the CP diet (a diet containing 5% cholestyramine and 0.1% pravastatin)-induced new species of 37-kDa mevalonate pyrophosphate decarboxylase (MPD) was characteristically and immunologically very similar to the well-known 45-kDa MPD. In the present study, we found a difference in subcellular distribution between 45- and 37-kDa MPD by cell fractionation and immunoblot analysis. The cytosol fraction contained 45- and 37-kDa MPD. Peroxisomal fraction contained a small amount of 45-kDa MPD, but not 37-kDa MPD. Also, 45-kDa MPD in peroxisome is localized in the matrix. From these data, the difference in subcellular distribution between 45- and 37-kDa MPD may be due to differences in the physiological role of cholesterol biosynthesis in rat liver.
  • Nobuyuki HORIE, Yukinori KOMADA, Yumiko UETA, Tomoko SUZUKI, Ryushi NO ...
    2001 年 24 巻 12 号 p. 1351-1355
    発行日: 2001年
    公開日: 2002/06/28
    ジャーナル フリー
    HL-60 cells differentiate into granulocyte-like cells by all-trans retinoic acid (ATRA) treatment, and the cellular proliferation is markedly reduced during the differentiation. To elucidate the molecular mechanisms of the growth arrest during the cellular differentiation, we examined the regulated expression of the thymidylate synthase (TS) gene. Northern blot analysis revealed that the expression of the TS gene was almost suppressed in the differentiated HL-60 cells. The change in the levels of nuclear factors, NF-TS2 and NF-TS3, that bind to the 5'-terminal regulatory region of the human TS gene was examined during the differentiation of the HL-60 cells. The amount of NF-TS2 did not change significantly during the differentiation, whereas that of NF-TS3 clearly increased as the cells differentiated. We previously reported that NF-TS2 and NF-TS3 bind to the sequence around the initiation codon ATG of the human TS gene. Further analyses revealed that the DNA sequences of NF-TS2 and NF-TS3 are very similar, and the first and second positions of the ATG triplet codon are important for the formation of rigid DNA-protein complexes. The present findings concerning the binding site and changes during the differentiation induced by ATRA treatment are very similar to those previously reported on the differentiation induced by 1,25-dihydroxyvitamin D3 treatment. These findings suggest that NF-TS3 is involved in regulating the expression of the human TS gene during the differentiation of HL-60 cells, regardless of the terminal cell type: macrophage-like cells or granulocyte-like cells.
  • Akihiro SANDA, Akihiko UCHIDA, Tadashi ITAGAKI, Hiroko KOBAYASHI, Nori ...
    2001 年 24 巻 12 号 p. 1356-1361
    発行日: 2001年
    公開日: 2002/06/28
    ジャーナル フリー
    A trypsin inhibitor that is highly homologous with bovine pancreatic trypsin inhibitor (BPTI) was co-purified along with RNase from Spirometra (Spirometra erinaceieuropaei). The amino acid sequence of this inhibitor (SETI) and the nucleotide sequence of the cDNA encoding this protein were determined by protein chemistry and gene technology. SETI contains 68 amino acid residues and has a molecular mass of 7798 Da. SETI has 31 amino acid residues that are identical with BPTI’s sequence, including 6 half-cystine and 5 aromatic amino acid residues. The active site Lys residue in BPTI is replaced by an Arg residue in SETI. SETI is an effective inhibitor of trypsin and moderately inhibits α-chymotrypsin, but less inhibits elastase or subtilisin. SETI was expressed by E. coli containing a PelB vector carrying the SETI encoding cDNA; an expression yield of 0.68 mg/l was obtained. The phylogenetic relationship of SETI and the other BPTI-like trypsin inhibitors was analyzed using most likelihood inference methods.
  • Eiji OTSUBO, Tsunetomo TAKEI, Masato NOMURA
    2001 年 24 巻 12 号 p. 1362-1365
    発行日: 2001年
    公開日: 2002/06/28
    ジャーナル フリー
    We previously reported that a human analogue of pulmonary surfactant protein-C (SP-C), SP-CL16 (6—28), with 23 residues (Fig. 1) was the most active analogue in a reconstituted lipid mixture and had the shortest chain among the poly-leucine-analogues examined. In the present study, we examined a new method of preparing this analogue, that is, stepwise solid-phase synthesis employing the Fmoc method followed by centrifugal partition chromatography (CPC) using an n-hexane/CH3OH/H2O/trifluoroacetic acid (TFA) (1000:1000:1:2, v/v) solvent system according to the descending method. The synthetic peptides were identified by matrix-assisted laser desorption ionization time-of-flight (MALDI-TOF) mass spectrometry in search of activity to improve the in vitro surface activity of a ternary lipid mixture composed of dipalmitoylphosphatidylcholine, egg-phosphatidylglycerol and palmitic acid (75:25:10, w/w) in a Langmuir-Wilhelmy surface balance. SP-CL16 (6—28) seemed comparable in surface activity with Surfacten® (Surfactant-TA), a modified surfactant preparation which has been used for the treatment of respiratory distress syndrome.
  • Masanori IWAMA, Yuko OGAWA, Kazuko OHGI, Tsutomu TSUJI, Masachika IRIE
    2001 年 24 巻 12 号 p. 1366-1369
    発行日: 2001年
    公開日: 2002/06/28
    ジャーナル フリー
    The anti-tumor activity of sialic acid binding lectin from Rana catesbeiana (cSBL) was increased by chemical modification with a water-soluble carbodiimide (EDC) in the presence of nucleophiles such as ethylenediamine and glycine methylester. Investigations on ribonuclease (RNase) activities of the modified cSBLs were conducted to elucidate the fundamental mechanisms underlying enhancement of the anti-tumor activity conferred by these modifications. The following three characteristics were observed with modification. (i) RNase activity of the modified cSBL was enhanced towards double stranded RNA and RNA-oligo dA hybrids. The activity increase was observed even under physiologic ionic strength conditions; (ii) RNase activity of the modified cSBL towards single stranded RNA and poly U decreased, while the activity towards poly C was unaffected; (iii) the base preference of the B2 base recognition site of modified cSBL decreased for guanine. On the contrary, the preference for cytosine and adenine increased. This result may explain why the RNase activity towards poly C was not affected by EDC-modification as mentioned above.
Notes
  • Akihiro MICHIHARA, Makoto SAWAMURA, Yukio YAMORI, Kenji AKASAKI, Hiros ...
    2001 年 24 巻 12 号 p. 1417-1419
    発行日: 2001年
    公開日: 2002/06/28
    ジャーナル フリー
    We carried out a comparison of tissue distribution of mevalonate pyrophosphate decarboxylase (MPD) between normotensive Wistar Kyoto rat (WKY) and stroke-prone spontaneously hypertensive rat (SHRSP) using Western blotting. However, there was no difference in tissue distribution of MPD between WKY and SHRSP, expect in brain and liver. We then compared the MPD between WKY and SHRSP liver at several weeks of age. We found that MPD in the liver as well as brain of SHRSP was significantly reduced from two weeks of age. This data is useful to identify or understand the mechanism underlying the reduced amount of MPD in SHRSP.
  • Toyoko KATAYAMA, Katsuro MIYAGAWA, Tohru KODAMA, Shinzo OIKAWA
    2001 年 24 巻 12 号 p. 1420-1422
    発行日: 2001年
    公開日: 2002/06/28
    ジャーナル フリー
    By a cell-based screening of an in-house natural product library, trichorzin HA V, belonging to a peptaibol family, was isolated from a strain of fungus Trichoderma as a calcitonin (CT) agonist. Like CT, trichorzin HA V elevated cAMP levels in T47D cells which endogenously express the human CT receptor. It also stimulated cAMP formation in cells expressing recombinant human CT receptor, but not in those that do not express the receptor, suggesting that it selectively interacts with the CT receptor. In contrast to trichorzin HA V, alamethicin, another well-characterized peptaibol, showed no cAMP-elevating activity at all. These results suggest that, although there was little amino acid sequence similarity between trichorzin HA V and CT, the biological activity of trichorzin HA V can mimic that of CT, acting via the CT receptor.
  • Hidemitsu PAN-HOU, Masako KIYONO, Tomoka KAWASE, Tomoko OMURA, Ginro E ...
    2001 年 24 巻 12 号 p. 1423-1426
    発行日: 2001年
    公開日: 2002/06/28
    ジャーナル フリー
    To evaluate the utility of polyphosphate kinase gene (ppk)-specified polyphosphate in mercury remediation, a fusion plasmid, pMK27, with ppk from Klebsiella aerogenes and mercury transport genes, merT and merP, from Pseudomonas K-62, was constructed. The transcription and translation of ppk, merT and merP were found to be mercury-inducible. The ppk-specified polyphosphate was identified in cells preinduced by Hg2+, but not in cells without mercury induction, suggesting that the synthesis of polyphosphate is regulated by merR. The hyper-sensitive phenotype to Hg2+, shown by bacteria with pMRD141, which contains merT and merP, was almost completely restored to its original levels when the ppk was introduced into the plasmid, suggesting that the Hg2+-toxicity was reduced by the polyphosphate, probably via chelation formation. Bacteria with pMK27 accumulated approximately 6-fold more mercury than the bacteria with cloning vector, pUC119. These results clearly demonstrate that the polyphosphate is capable of retaining mercury in the cells without taxing the cells. Based on the results obtained in the present study, the fusion plasmid pMK27 may serve as a strategy for mercury remediation.
Pharmacology
Regular Articles
  • Tomohiro MANABE, Atsuko YAMAMOTO, Kumi SATOH, Kazuo ICHIHARA
    2001 年 24 巻 12 号 p. 1370-1372
    発行日: 2001年
    公開日: 2002/06/28
    ジャーナル フリー
    We examined the development of tolerance to nitroglycerin (glyceryl trinitrate; GTN) in the rat when isosorbide-5-mononitrate (ISMN) or GTN was continuously infused. Under pentobarbital anesthesia (60 mg/kg, i.p.), mean arterial blood pressure was measured via the left common carotid artery. Bolus injection of ISMN (0.25—250 mg/kg) and GTN (0.25 μg/kg—2.5 mg/kg) was made into the right external jugular vein. ISMN (2.5 mg/h/rat for 7 d), GTN (1.3 μg/h/rat for 7 d), or GTN (0.2 mg/h/rat for 3 d) was infused continuously using an osmotic pump embedded subcutaneously. Bolus injection of ISMN and GTN decreased arterial blood pressure in a dose-dependent manner. The hypotensive effect of ISMN was 2000 times less potent than that of GTN. The GTN-induced hypotensive effect was not affected after continuous infusion of ISMN, whereas it was attenuated after continuous infusion of GTN at either dose. Chronic treatment with ISMN does not induce GTN tolerance as easily as treatment with GTN.
  • Toan-Thang PHAN, Lingzhi WANG, Patrick SEE, Renee Jacqueline GRAYER, S ...
    2001 年 24 巻 12 号 p. 1373-1379
    発行日: 2001年
    公開日: 2002/06/28
    ジャーナル フリー
    Extracts from the leaves of Chromolaena odorata have been shown to be beneficial for treatment of wounds. The crude ethanol extract of the plant had been demonstrated to be a powerful antioxidant to protect fibroblasts and keratinocytes in vitro. In this study, the most active compounds were fractionated and identified from the crude extract using liquid chromatography coupled with UV spectroscopy and mass spectrometry. The antioxidant effects of purified fractions on cultured fibroblasts and keratinocytes were investigated using colorimetric and lactate hydrogenase release assay. The results showed that the phenolic acids present (protocatechuic, p-hydroxybenzoic, p-coumaric, ferulic and vanillic acids) and complex mixtures of lipophilic flavonoid aglycones (flavanones, flavonols, flavones and chalcones) were major and powerful antioxidants to protect cultured skin cells against oxidative damage. In conclusion, the extract from C. odorata contains a mixture of powerful antioxidant compounds that may be one of potential mechanism contributing to enhanced wound healing.
Notes
  • Akiko SOYAMA, Yoshiro SAITO, Nobumitsu HANIOKA, Norie MURAYAMA, Osamu ...
    2001 年 24 巻 12 号 p. 1427-1430
    発行日: 2001年
    公開日: 2002/06/28
    ジャーナル フリー
    By sequencing genomic DNA from 73 established cell lines derived from Japanese individuals, we detected 9 single nucleotide polymorphisms (SNPs) in the CYP2C8 gene. Of them, 3 exonic SNPs resulted in amino acid alterations (g416a, R139K; a1196g, K399R; c1210g, P404A). The first two alterations were detected concurrently in one cell line and thought to be the same as CYP2C8*3. To examine the effects of these amino acid alterations on CYP2C8 function, wild-type and four types of variant CYP2C8 cDNA constructs (R139K, K399R, R139K/K399R and P404A) were transfected into Hep G2 cells and their paclitaxel 6α-hydroxylase activities were determined in vitro. Km values were not significantly different from that of the wild-type in any of the variants studied. The variant R139K/K399R showed reduced values for Vmax and clearance (Vmax/Km) similar to those of its single variant, R139K. The variant P404A also showed a significantly lowered clearance due to reduced level of protein expression. These results suggest that not only the double variant (R139K/K399R, CYP2C8*3) but also our novel variant P404A in the CYP2C8 gene are less efficient in paclitaxel metabolism.
  • Yumi SUGIMOTO, Tomoko YOSHIKAWA, Toshiko NOMA, Jun YAMADA
    2001 年 24 巻 12 号 p. 1431-1433
    発行日: 2001年
    公開日: 2002/06/28
    ジャーナル フリー
    Effects of the 5-HT2C/2B receptor agonist m-chlorophenylpiperazine (mCPP) on hyperphagia elicited by 2-deoxy-D-glucose (2-DG) were investigated in rats. mCPP apparently reduced 2-DG-induced hyperphagia. Suppressive effects of mCPP on hyperphagia induced by 2-DG were inhibited by the 5-HT2A/2B/2C receptor antagonist, ritanserin, although the 5-HT2A receptor antagonist ketanserin was without effect. Thus, inhibitory effects of mCPP on 2-DG-induced hyperphagia are mediated by the 5-HT2C/2B receptor. Our results demonstrate that mCPP can inhibit the bulimia model, 2-DG-induced hyperphagia.
  • Matsumi YAMAZAKI, Kazuhiro HIRAKURA, Yukinori MIYAICHI, Kimiaki IMAKUR ...
    2001 年 24 巻 12 号 p. 1434-1436
    発行日: 2001年
    公開日: 2002/06/28
    ジャーナル フリー
    Polyacetylenic alcohols and their linoleates isolated from Panax ginseng C.A. Meyer and Cirsium japonicum DC., of which the lipophilic extracts had been found to affect the neuritogenesis of cultured paraneurons, were demonstrated to have a significant neuritogenic effect on PC12h and Neuro2a cells. Panaxynol and the acetylenic triol in particular were highly efficient at concentrations ≥2 μM. Panaxynol (20 mg/kg/d, i.p., for 3 d) was confirmed to improve scopolamine-induced memory deficit in mice (Y-maze task). It is suggested that the promotion of neuritogenesis in cultured paraneurons by the addition of panaxynol is related its ability to improve memory deficits in animals.
  • Masayoshi YAMAGUCHI, Zhong Jie MA
    2001 年 24 巻 12 号 p. 1437-1439
    発行日: 2001年
    公開日: 2002/06/28
    ジャーナル フリー
    The effect of various polyphenols on calcium content and alkaline phosphatase activity in the femoral-diaphyseal and -metaphyseal tissues of young rats in vitro was investigated. Bone tissues were cultured for 24 h in serum-free Dulbecco’s modified Eagle’s medium containing either vehicle or various polyphenols (10-7—10-4 M). The presence of genistein (10-6—10-4 M) caused a significant increase in calcium content and alkaline phosphatase activity in the femoral-diaphyseal and -metaphyseal tissues. Resveratrol (10-4 M) decreased metaphyseal calcium content significantly, and it (10-6—10-4 M) had a significant inhibitory effect on diaphyseal enzyme activity. Epigallocatechin gallate (EGCg; 10-4 M) significantly inhibited alkaline phosphatase activity in the diaphyseal and metaphyseal tissues. EGCg (10-7—10-4 M) had no effect on bone calcium content. Meanwhile, glycitein, quercetin, or catechin in the range of 10-7 to 10-4 M did not have an effect on calcium content and alkaline phosphatase activity in the femoral-diaphyseal and -metaphyseal tissues. The present study suggests that a phytoestrogen genistein has a unique anabolic effect on bone calcification in vitro.
Toxicology
Regular Articles
  • Sang-Han LEE, Eun-Soo YOUK, Young Jin JEON, Sang Bae HAN, Hyoung-Chin ...
    2001 年 24 巻 12 号 p. 1380-1383
    発行日: 2001年
    公開日: 2002/06/28
    ジャーナル フリー
    We prove here that serum albumin inhibits apoptosis induced by polychlorinated biphenyls (PCBs), confirming that serum albumin binds to PCB, and that the albumin-PCB complexes inhibit apoptosis in HL-60 cells. We found that PCB (50 μM) increased the activity of caspase-3-like protease when HL-60 cells, as well as splenocytes, were cultured in “serum-free medium.” Benzyloxycarbonyl-Val-Ala-Asp-fluoromethylketone (Z-VAD-fmk) inhibited apoptosis in cells cultured in the serum-free medium containing 50 μM PCB. To elucidate whether or not PCBs induce apoptosis in vivo, we examined apoptosis of splenocytes by administering PCB to ICR mice (100, 500, 1000 mg·kg-1·d-1) for 5 d and characterizing splenocytes. Interestingly, splenocytes treated with PCB did not show any changes characteristic of apoptosis. These results demonstrate that PCB activates the caspase-3-like death protease in vitro in serum-free medium, but does not induce apoptosis of splenocytes in vivo, suggesting that blood serum may mask the apoptosis induced by PCB.
  • Kazuhiro SAISHO, Karen S. SCOTT, Shigeyoshi MORIMOTO, Yuji NAKAHARA
    2001 年 24 巻 12 号 p. 1384-1388
    発行日: 2001年
    公開日: 2002/06/28
    ジャーナル フリー
    In order to study the incorporation of sildenafil (SDF) and its N-demethylated metabolite (norSDF) into hair, animal model experiments were carried out. After shaving the back hair, SDF was dosed to two sets of three male dark-agouti pigmented rats (5 weeks old) per each group at 25 mg/kg once a day for 5 successive days with intraperitoneal (i.p.) (set1) and oral administration (set2). The regrown back hair was collected 14 d after the first administration. Three typical extraction methods, using methanol-5 M hydrochloric acid, methanol-trifluoroacetic acid and 1 M sodium hydroxide, were evaluated using the rat hair samples containing SDF and norSDF. Methanol-5 M hydrochloric acid was the best extraction method in terms of high efficiency and reproducibility. The extract was purified using Bond Elut Certify columns and was derivatized withtrimethylsilylimidazole:N,O-bis(trimethylsilyltrifluoroacetamide):trimethylchlorosilane (3:3:2) at 90°C for 30 min. The trimethylsilylated products were analyzed by GC-MS using selected ion monitoring. SDF and norSDF were simultaneously detected in the rat hair. The hair concentrations were 4.9—6.3 (av. 5.8) ng/mg and 15.6—20.3 (av. 17.6) ng/mg for SDF and norSDF, respectively, with i.p. administration, and 2.6—4.1 (av. 3.6) ng/mg and 8.1—10.4 (av. 9.1) ng/mg with oral administration. The hair concentrations of norSDF were about three times higher than those of SDF, and the ratios of both compounds showed no significant difference between i.p. and oral administrations. This method was applied to the scalp hair of two patients who orally took SDF at regular intervals for the treatment of penile erectile dysfunction. The hair concentrations of SDF and norSDF in the two patients were 19.8 and 55.9 ng/mg, and 1.7 and 5.6 ng/mg, respectively.
Pharmacognosy
Regular Articles
  • Hui CAO, Yohei SASAKI, Hirotoshi FUSHIMI, Katsuko KOMATSU
    2001 年 24 巻 12 号 p. 1389-1394
    発行日: 2001年
    公開日: 2002/06/28
    ジャーナル フリー
    Curcuma drugs have been used discriminatingly for invigorating blood circulation, promoting digestion, and as a cholagogic in China. However, there is confusion about the drug’s botanical origins and clinical uses because of morphological similarity of Curcuma plants and drugs. In order to develop an ultimate identification, molecular analysis based on 18S rRNA gene and trnK gene sequences were performed on 6 Curcuma species used medicinally in China and Japan. The 18S rRNA gene sequences were found to be of 1810 bps in length. In comparison with the common sequence of C. longa, C. phaeocaulis, C. wenyujin and C. aromatica, that of C. kwangsiensis had one base substitution, and the same base difference was observed between the Chinese and the Japanese populations of C. zedoaria. The trnK gene sequences were found to span 2698—2705 bps. There were base substitutions, small deletions or insertions at some sites between the trnK coding region and matK region among each species. Based on the base substitutions, C. zedoaria and C. kwangsiensis specimens were divided into two groups, respectively. An identical sequence was detected in C. phaeocaulis and in the Chinese population of C. zedoaria, as well as in the Japanese population of C. zedoaria and in one group of C. kwangsiensis with a purple-colored band in leaves. New taxonomic information to be used for authenticating Curcuma drugs was obtained.
  • Ju-Xiu HE, Teruaki AKAO, Takao NISHINO, Tadato TANI
    2001 年 24 巻 12 号 p. 1395-1399
    発行日: 2001年
    公開日: 2002/06/28
    ジャーナル フリー
    The influence of synthetic drugs prescribed for peptic ulcer on the pharmacokinetic fate of glycyrrhizin (GL) from Shaoyao-Gancao-tang (SGT, a traditional Chinese formulation, Shakuyaku-Kanzo-to in Japanese) was investigated in rats. Co-administration of histamine H2-receptor antagonist (cimetidine) and anticholinergic drug (scopolamine butyl bromide) with SGT didn’t influence the area under the plasma concentration-time curves (AUC) of glycyrrhetic acid (GA), an active metabolite derived from GL in SGT. The AUC of GA from SGT were significantly reduced by co-administration of synthetic drugs commonly used for peptic ulcer in a triple therapy (OAM), a combination of a proton pump inhibitor (omeprazole) and two antibiotics (amoxicillin and metronidazole). We found that the reduction of AUC in OAM treatment was due to the antibacterial effect of amoxicillin and metronidazole on intestinal bacteria in rat which lead to the decrease of GL-hydrolysis activity. The present study suggests that it may not be a proper way to use triple therapy containing antibiotics simultaneously with SGT for healing of chronic ulcers.
  • Tadashi KIHO, Mari KOCHI, Shigeyuki USUI, Kazuyuki HIRANO, Koichi AIZA ...
    2001 年 24 巻 12 号 p. 1400-1403
    発行日: 2001年
    公開日: 2002/06/28
    ジャーナル フリー
    Continuous oral administration of the acidic polysaccharide (TAP) solution (0.5 g/l) and the TAP-H (degradation products of TAP) solution (1.5 g/l) instead of water for 10 weeks were found to depress plasma glucose increases in diabetes using genetically non-insulin-dependent diabetic model (KK-Ay) mice. TAP and TAP-H significantly lowered levels of insulin, total-cholesterol and triglyceride in the blood of the mice. In excretion to feces, TAP and TAP-H significantly increased the total bile acid, while the cholesterol content of both groups was less than that of the control. Furthermore, TAP and TAP-H significantly decreased the plasma lipoperoxide level. The study shows that TAP and TAP-H have an antidiabetic effect on diabetes model mice.
Notes
  • Takao KONOSHIMA, Tenji KONISHI, Midori TAKASAKI, Kiyonori YAMAZOE, Har ...
    2001 年 24 巻 12 号 p. 1440-1442
    発行日: 2001年
    公開日: 2002/06/28
    ジャーナル フリー
    Eight new diterpenoids (1—8) have been isolated from the wood of Excoecaria agallocha (Euphorbiaceae) and their inhibitory effects on the induction of Epstein-Barr virus early antigen (EBV-EA) in Raji cells were examined to search for potent anti-tumor-promoters from natural resources. Of these compounds, the secolabdane-type diterpenoid, compound 7 exhibited a remarkable inhibitory effect on EBV-EA induction, and a significant anti-tumor-promoting effect in the mouse two-stage carcinogenesis test using 7,12-dimethylbenz[a]anthracene and 12-O-tetradecanoyl-phorbol-13-acetate.
  • Junei KINJO, Tsuneatsu NAGAO, Takashi TANAKA, Gen-ichiro NONAKA, Hikar ...
    2001 年 24 巻 12 号 p. 1443-1445
    発行日: 2001年
    公開日: 2002/06/28
    ジャーナル フリー
    The MeOH extract of the seeds of Rhynchosia volubilis (Leguminosae) showed antiproliferative activity against human gastric adenocarcinoma [MK-1, 50% growth inhibition (GI50): 25 μg/ml], human uterus carcinoma (HeLa, GI50: 30 μg/ml), and murine melanoma (B16F10, GI50: 8 μg/ml) cells. Bioactivity-guided fractionation resulted in the isolation of gallic acid methylester (1), gallic acid (2), 7-O-galloylcatechin (3), 1,6-di-O-galloylglucose (4), 1-O-galloylglucose (5), and trigalloylgallic acid (6), and their antiproliferative activity was estimated. All showed much stronger inhibition against B16F10 cell growth than against HeLa and MK-1 cell growth. Compound 2 and its tetramer (6) with a free carboxyl group showed higher activity than those which did not have a free carboxyl group. In relation to the gallic acid tetramer (6), two gallic acid dimers (ellagic acid and dehydrodigallic acid) and trimers (tergallic acid dilactone and flavogallonic acid dilactone) were tested for their activity, and compared with those of the isolates.
Biopharmacy
Regular Articles
  • Yuhsuke OHKAWA, Yasunori KIYOHARA, Tomoyuki ASOH, Hiroshi MAEDA, Masat ...
    2001 年 24 巻 12 号 p. 1404-1410
    発行日: 2001年
    公開日: 2002/06/28
    ジャーナル フリー
    The effects of 4-hydroxyantipyrine (4-OH), a major metabolite of antipyrine and its sulfate, 4-hydroxyantipyrine O-sulfate (4-S), on the pharmacokinetics of citicoline and thiopental sodium were investigated in rats. The concomitant use of 4-OH increased significantly the tissue-to-plasma concentration ratio (Kp) of citicoline in the brain and liver and that of thiopental sodium in the brain, liver, and heart, while 4-S did not affect them. The permeability clearance of blood-brain barrier (BBB) (Kin) and the total distribution volume (Vdbr) of citicoline were not affected by either 4-OH or 4-S. However, those of thiopental sodium were significantly increased by not only 4-OH but also by 4-S. On the other hand, the plasma concentration of antipyrine was significantly decreased by the intravenous bolus coadministration of N-acetyl-p-aminophenyl O-sulfate (APAPS) at steady-state plasma concentration of antipyrine. A similar reduction was not observed with the intravenous coadministration of acetaminophen (APAP). The Kp value of antipyrine was significantly increased in the brain by the coadministration of APAPS, but was not affected by APAP. The increment in the drug distribution to the brain with the concomitant use of 4-OH (or APAPS) observed in this study is useful information for the application of drug combinations as biodistribution promoters.
  • Alfredo GARCÍA-ARIETA, Santiago TORRADO-SANTIAGO, Luis GOYA, Ju ...
    2001 年 24 巻 12 号 p. 1411-1416
    発行日: 2001年
    公開日: 2002/06/28
    ジャーナル フリー
    The aim of this work is to describe and characterize a new spray-drying procedure for the production of nasal powders as an alternative to the conventional freeze-drying method. Cyanocobalamin was chosen as the active ingredient and loaded into five different nonsoluble vehicles with high water absorption ability. Then these hydrated particles were suspended in methylene chloride and spray-dried. Particle size, morphology, true, bulk and tapped density, percentage of compressibility, moisture content, water intake, and drug diffusion were studied and significant differences were obtained depending on the nature of the vehicle. The drying method, either the new spray- or the conventional freeze-drying, was less important. Interestingly, an inverse correlation was found between water uptake and drug diffusion. Microcrystalline cellulose, dextran microspheres, and crospovidone were chosen for an in vivo bioavailability study in rabbits. Three other nasal reference formulations and an intravenous solution were also administered. The spray-dried powders showed higher bioavailability than the three nasal reference formulations. The highest absorption enhancement was observed with cellulose microcrystalline powders, which provided a 25% mean absolute bioavailability, followed by crospovidone and dextran microspheres formulations with mean bioavailability values of 14% and 7%, respectively. In conclusion, the new spray-drying method is useful for the production of cyanocobalamin nasal powders.
Notes
  • Ayako OHNISHI, Yoshitaka YANO, Kenji SHIMAMURA, Takayoshi OGUMA
    2001 年 24 巻 12 号 p. 1446-1450
    発行日: 2001年
    公開日: 2002/06/28
    ジャーナル フリー
    To assess the usefulness of the population pharmacokinetic parameters of vancomycin (VCM) based on a two-compartment model in Japanese adult patients, predictability by a Bayesian method was evaluated using a concentration time course after single dosing to 22 patients with various degrees of renal function. Using one or two points from the observed data for each patient, the concentrations predicted by a Bayesian method were compared with the observed data for each sampling time. The patients were separated into five groups based on their renal functions indicated by creatinine clearance, and the mean prediction error (MPE) and root mean squared error (RMSE) were calculated for each group as measures of accuracy and precision, respectively. In both one- and two-point methods, the absolute MPE values at each sampling time in the elimination phase were less than 2.5 μg/ml, and the RMSE values were also small. No clear differences were found in MPE and RMSE among the groups. In the distribution phase, the MPE and RMSE were somewhat greater, and RMSE in some groups was around 15 μg/ml when trough data was used to predict the peak concentration. Also, the theoretical RMSE using this population parameter setting could well explain the observed RMSE. These results confirmed this population parameter setting is useful for at least predicting concentration in the elimination phase after single dosing, and the predictability was independent of renal function.
Miscellaneous
Notes
  • Dae-Won LEE, Chanhong KIM, Dong-Ung LEE
    2001 年 24 巻 12 号 p. 1451-1453
    発行日: 2001年
    公開日: 2002/06/28
    ジャーナル フリー
    Gagaminine, a steroidal alkaloid isolated from the roots of Cynanchum wilfordii, exhibited potent inhibitory effects on the aldehyde oxidase activity and lipid peroxidation. To find a possible means of mass production of this active component, which will be useful for animal tests, we synthesized it by an in vitro culture method using various growth conditions. Calli were induced from the explants of this medicinal plant and cultivated under culture conditions which varied in light, and the kinds and concentration of plant growth regulators. The production of gagaminine was found to be significantly higher in the dark than in the light. The best gagaminine content (0.960%) was obtained after cultivation of stems on the medium containing 2,4-dichlorophenoxyacetic acid (2,4-D, 2.0 mg/l) only. However, gagaminine was not detected by the mixture of 2,4-D and kinetin, while the mixtures of 2,4-D/zeatin and 2,4-D/6-benzylaminopurine produced a low content of gagaminine (<0.4%). In addition, suspension medium was much better for the formation of gagaminine than solid medium with an increase from 0.960 to 2.227% yield. These results suggest that gagaminine can be produced massively by in vitro culture using stems under the conditions of dark and 2,4-D on liquid medium.
  • Matsumi YAMAZAKI, Naoki SAKURA, Kenzo CHIBA, Tetsuro MOHRI
    2001 年 24 巻 12 号 p. 1454-1455
    発行日: 2001年
    公開日: 2002/06/28
    ジャーナル フリー
    Genipin, which was shown in our previous investigation to have prominent neuritogenic activity in paraneurons such as PC12h cells, was studied to determine whether it could prevent the toxicity of Alzheimer’s amyloid β protein (Aβ) in cultured hippocampal neurons. Increased release of lactate dehydrogenase from hippocampal neurons after 2 d of Aβ25-35 administration was prevented dose dependently by the addition of genipin 20—40 μM. Morphological observations and trypan blue staining of cells confirmed the protection of hippocampal neurons from Aβ toxicity by genipin. Geniposide had less effect in preventing Aβ toxicity.
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