Biological and Pharmaceutical Bulletin
Online ISSN : 1347-5215
Print ISSN : 0918-6158
ISSN-L : 0918-6158
25 巻 , 2 号
選択された号の論文の26件中1~26を表示しています
Review
  • Toshikiro Kimura, Kazutaka Higaki
    原稿種別: Review
    専門分野: [not specified]
    2002 年 25 巻 2 号 p. 149-164
    発行日: 2002年
    公開日: 2002/04/27
    ジャーナル フリー
    The gastrointestinal (GI) absorption of orally administered drugs is determined by not only the permeability of GI mucosa but also the transit rate in the GI tract. It is well known that the gastric emptying rate is an important factor affecting the plasma concentration profile of orally administered drugs, and the intestinal transit rate also has a significant influence on the drug absorption, since it determines the residence time of the drug in the absorption site. The reason why the residence time is also a critical factor for drug absorption is that there is the site difference in absorbability for some drugs. We have developed the GI-Transit-Absorption Model (GITA Model) to analyze and predict the drug absorption kinetics by taking into account both the two factors, i.e. GI transit and drug absorbability including its site difference. GITA Model has been already evidenced to be very useful for estimating the absorption kinetics of drugs with various characteristics and applied to assess the human data in combination with the gamma scintigraphy. In this review, the importance of GI transit rate in determining the absorption kinetics and the bioavailability of orally administered drugs is discussed mainly employing GITA Model and the results obtained by the model.
Analytical Biochemistry
Regular Articles
Biochemistry/Molecular Biology
Regular Articles
  • Takaharu Negoro, Kazue Satoh, Fumio Iinuma, Takashi Tobe, Mitsuo Watan ...
    原稿種別: Regular Article
    専門分野: Biochemistry/Molecular Biology
    2002 年 25 巻 2 号 p. 172-178
    発行日: 2002年
    公開日: 2002/04/27
    ジャーナル フリー
    Among the eight inbred mouse strains employed in our preceding report, 12-O-tetradecanoylphorbol 13-acetate (TPA) painting alone induced CD4+ regulatory T (Tr) cells in four strains (e.g., C3H/He) at 6—8 weeks of age, but not in the remaining strains (e.g., C57BL/6, BALB/c). In the present study, the effect of growth from 4—14 weeks on delayed-type hypersensitivity (DTH) response was investigated in three inbred murine strains, C3H/He (H-2k), C57BL/6 (H-2b) and BALB/c (H-2d) mice. In all strains older than 10 weeks, DTH response was suppressed exclusively by TPA painting. The defect of suppressive activity for DTH in several of the strains at 6—8 weeks of age was dependent on the presence of cells, which blocked regulatory cell activity at 6—8 weeks of age, but not at 10 weeks of age. The age-dependent difference in regulatory activity was caused by the presence of CD8+ contra-regulatory T (Tcr) cells. CD8+ contra-regulatory T cells are required to contact regulatory cells in order to block DTH suppressive activity. Adhesion molecules were of great importance in contra-suppression, as antibody treatment to LFA-1 or ICAM-1 blocked this activity. ICAM-1 expression on CD4 T cells greatly increased following growth in 10 week-BALB/c mice receiving TPA than 6-week-old mice, however, a slight increase in growth occurred in 6-to-10-week-old animals in which TPA was absent. The degree of increment in body weight was very similar in these inbred strains. Thymus involution in C3H/He mice was the earliest signal among these mice. This result may suggest that the period of differentiation and maturation of T cells in a first lymphoid tissue for the growth process differs in these three inbred strains. This study provides an interesting example of genetic control of maturation or proliferation of peripheral T cells.
  • Yuichi Kawai, Takaomi Yamaguchi, Takahiro Yoden, Motoki Hanada, Masaha ...
    原稿種別: Regular Article
    専門分野: Biochemistry/Molecular Biology
    2002 年 25 巻 2 号 p. 179-183
    発行日: 2002年
    公開日: 2002/04/27
    ジャーナル フリー
    Protein phosphorylation plays many important roles in cell functions and cell differentiation. To clarify the roles of protein phosphorylation in early embryonic development in mice, 2-cell embryos were cultured in the presence of various protein phosphatase inhibitors such as calyculin A, okadaic acid, cyclosporin A, tacrolimus (FK506) and benzyl-phosphonic acid. Calyculin A potently inhibited the 2-cell cleavage to the 4-cell stage. The concentration for 50% inhibition was 0.26 nM. At the same time, we found that calyculin A-treated 2-cell embryos showed a morula-like shape at a concentration of 2 nM in 24 h. It is well known that E-cadherin plays a key role in the compaction of late 8-cell stage embryos. In this report, we observed the distribution of E-cadherin protein using anti-E-cadherin antibody with a fluorescence microscope, and also evaluated the relative E-cadherin mRNA content at various stages of embryos by RT-PCR and ABI PRISM 7700 System (a real time PCR apparatus). The fluorescence intensity of E-cadherin increased along with the embryonic development. During the embryonic development from the 2-cell stage to the blastocyst stage, the relative E-cadherin mRNA content greatly increased in a time-dependent manner, while the mRNA did not increase with the addition of calyculin A at the 2-cell stage. Therefore, we observed the localization of the E-cadherin protein in calyculin A-treated embryos with a laser microscope. The distribution pattern of E-cadherin was altered by the addition of calyculin A from a scattered pattern throughout the embryos to a localized pattern at the cell-cell boundary region. These results strongly suggest that the distribution of E-cadherin protein is regulated by protein phosphorylation and/or dephosphorylation.
Notes
  • Toshiro Niwa, Yumi Maekawa, Megumi Fujimoto, Kae Kishimoto, Yoshiyasu ...
    原稿種別: Note
    専門分野: Biochemistry/Molecular Biology
    2002 年 25 巻 2 号 p. 235-238
    発行日: 2002年
    公開日: 2002/04/27
    ジャーナル フリー
    Effect of nonylphenol on aminopyrine N-demethylase activity, a typical drug-metabolizing enzyme activity, by ten kinds of human hepatic cytochrome P450s (CYP) and on progesterone 17α-hydroxylase activity by steroidogenic CYP17 was investigated. When determined at 2 mM substrate concentration, nonylphenol (1 mM) most efficiently inhibited aminopyrine N-demethylation by CYP2C9 and CYP2C19, by 61% and 59%, respectively, followed by CYP2D6, CYP1A2, CYP2C18 and CYP2C8 (46—51%), whereas inhibition of the activities by other CYPs was less than 27%. Additionally, nonylphenol competitively inhibited diclofenac 4′-hydroxylation by CYP2C9 and S-mephenytoin 4′-hydroxylation by CYP2C19 with Ki values of 5.3 and 37 µM, respectively. Furthermore, nonylphenol exhibited a competitive inhibition of progesterone 17α-hydroxylase activity by CYP17 with Ki value of 62 µM. These results suggest that nonylphenol inhibits human hepatic CYPs, especially CYP2C9 and CYP2C19, and steroidogenic CYP17 activities.
  • Noboru Uchide, Kunio Ohyama, Bo Yuan, Tomomi Sano, Toshio Bessho, Tosh ...
    原稿種別: Note
    専門分野: Biochemistry/Molecular Biology
    2002 年 25 巻 2 号 p. 239-243
    発行日: 2002年
    公開日: 2002/04/27
    ジャーナル フリー
    We examined the expression of mRNAs for inflammatory cytokines and Fas in cultured human fetal membrane cells responding to influenza virus (IV) infection using the reverse transcriptase-polymerase chain reaction (RT-PCR). Primary cultured chorion and amnion cells prepared from human fetal membranes were infected with IV. Chorion cells expressed significant amounts of interleukin (IL)-1β, IL-6, tumor necrosis factor (TNF)-α, interferon (IFN)-β, IFN-γ and granulocyte macrophage colony-stimulating factor (GM-CSF) mRNAs and small amounts of Fas mRNA in response to IV infection. Amnion cells expressed TNF-α and IFN-β mRNAs in response to IV infection, while expression of the other mRNAs was not altered. We also examined whether or not TNF-α, IFN-β, IFN-γ and Fas participated in IV infection-induced apoptotic DNA fragmentation in chorion cells. Neutralizing antibodies against them did not inhibit DNA fragmentation. These results suggested that chorion cells expressed significant amounts of mRNAs for inflammatory cytokines in response to IV infection, and that, in contrast, mRNA expression was quiescent in amnion cells. Moreover, TNF-α, IFN-β, IFN-γ and Fas do not appear to be directly involved in the apoptosis induction of IV-infected chorion cells. The results indicated that chorion cells may play a role in defense against IV through an antiviral immune response and apoptosis to eliminate own cells and viral pathogens in infected organs, whereas amnion cells do not play such a role.
Pharmacology
Regular Articles
  • Masayuki Takeuchi, Yasuaki Tatsumi, Kiyoyuki Kitaichi, Kenji Baba, Ryu ...
    原稿種別: Regular Article
    専門分野: Pharmacology
    2002 年 25 巻 2 号 p. 184-187
    発行日: 2002年
    公開日: 2002/04/27
    ジャーナル フリー
    It is well known that bronchial asthma is defined as chronic eosinophilic inflammation of the respiratory tract and that as one of the various types of inflammatory cells, eosinophils induce the airway inflammation of chronic asthma. Granulocyte-macrophage colony-stimulating factor (GM-CSF) has been shown to play an important role in the prolongation of the survival of eosinophils. We investigated the inhibitory effect of the selective phosphodiesterase (PDE) 4 inhibitors, 3,4-dipropyl-4,5,7,8-tetrahydro-3H-imidazo[1,2-i]purin-5-one (XT-611) and rolipram, and the nonselective PDE inhibitor theophylline, against GM-CSF-induced prolongation of the survival of eosinophils isolated from patients with bronchial asthma. Eosinophils (106 cells/ml) were incubated in the presence of GM-CSF together with or without theophylline, rolipram or XT-611 at 37 °C, and the viable cells were assessed up to 4 d using Trypan blue dye exclusion. The presence of theophylline (10−4 M), rolipram (10−4—10−5 M) or XT-611 (10−4—10−5 M) significantly reduced the GM-CSF (10 pg/ml)-induced prolongation of viability of eosinophils. These findings suggest that selective PDE 4 inhibitors, including XT-611, may effectively reduce the activities of inflammatory cells in the airway of bronchial asthma patients.
  • Koji Hayashi, Mikio Ito
    原稿種別: Regular Article
    専門分野: Pharmacology
    2002 年 25 巻 2 号 p. 188-192
    発行日: 2002年
    公開日: 2002/04/27
    ジャーナル フリー
    Recently, we reported that low molecular weight (LMW) chitosan (chitosan lactate, average MW: 20000) prevents the progression of low dose (100 mg/kg, i.p.) streptozotocin-induced slowly progressive diabetes mellitus in male ICR mice. The present study was designed to clarify the effects of LMW chitosan on hyperglycemia, hyperinsulinemia and hypertriglyceridemia in genetically obese diabetic male KK-Ay mice. LMW chitosan (0.05%, 0.2% or 0.8% water solution) was given daily as drinking water to male KK-Ay mice for 11 weeks, from 5 weeks of age. The non-fasting serum glucose levels of control mice continued to increase slowly throughout the experimental period. LMW chitosan lowered the serum glucose levels in a dose-dependent manner. In these diabetic mice, hyperinsulinemia and hypertriglyceridemia were observed, and LMW chitosan was dose-dependently effective in improving both serum biochemical parameters. LMW chitosan at three doses improved overdrinking and polyuria observed in these diabetic mice. It is concluded from these results that LMW chitosan may be useful for the treatment of obesity-related type 2 diabetes mellitus.
  • Jing Cai, Mingjie Liu, Zhao Wang, Yong Ju
    原稿種別: Regular Article
    専門分野: Pharmacology
    2002 年 25 巻 2 号 p. 193-196
    発行日: 2002年
    公開日: 2002/04/27
    ジャーナル フリー
    Dioscin, a saponin extracted from the root of Polygonatum Zanlanscianense Pamp, markedly inhibited proliferation of Hela cells. The results indicated that Hela cells underwent apoptosis in dose- and time-dependent manners when treated with Dioscin. Caspase-3, -8 and -9 activities were also detected. The low enzymatic activity of caspase-8 and high activity of caspase-9 showed that the mitochondrial pathway was activated in apoptosis. The reduced expression of the survival protein Bcl-2 also confirmed this result. These studies may be significant in finding a new drug to treat human cervical cancer.
  • Yoko Kubota, Keizo Umegaki, Naoko Tanaka, Hideya Mizuno, Kazuki Nakamu ...
    原稿種別: Regular Article
    専門分野: Pharmacology
    2002 年 25 巻 2 号 p. 197-200
    発行日: 2002年
    公開日: 2002/04/27
    ジャーナル フリー
    We investigated the effects of dietary supplements on atria isolated from male Wistar rats. The examined supplements, which are increasingly used in Japan, those were Ginkgo biloba extract (GBE), catechins, isoflavones, sodium iron chlorophyllin and sodium copper chlorophyllin. GBE at 100—1000 µg/ml significantly increased the beat rate and the contractile force. Catechins at 1—100 µg/ml significantly potentiated the contractile force but did not effect the beat rates. However, isoflavones, sodium iron and sodium copper chlorophyllins did not change the contractile force or the beat rates. To identify the active ingredient of GBE, ginkgolide B, quercetin and amentoflavone on the atria were tested. Ginkgolide B weakened the contractile force. Quercetin potentiated the contractile force at only 30 µg/ml. Amentoflavone significantly increased the beat rate. From these findings, amentoflavone and quercetin were considered to be the principal ingredients of GBE producing the positive chronotropic and inotropic actions, respectively. In the case of catechins, (−)-epigallocatechin gallate (EGCg), one of the principal ingredients, produced inotropic actions. These findings suggest that there are some dietary supplements which affect cardiac function, such GBE and catechins.
  • Katsunori Yamaura, Kohei Ogawa, Taeko Yonekawa, Tomonori Nakamura, Shi ...
    原稿種別: Regular Article
    専門分野: Pharmacology
    2002 年 25 巻 2 号 p. 201-205
    発行日: 2002年
    公開日: 2002/04/27
    ジャーナル フリー
    The causal relationship between the inhibition of antibody production and liver injury induced by single doses of acetaminophen (APAP) was investigated in mice. The liver injury and antibody production were evaluated using the serum transaminase activity and the number of antibody forming cells against sheep red blood cells (SRBC), respectively. The relevance of APAP hepatotoxicity with inhibiting antibody production was elucidated in fasted and fed mice treated with a single oral administration of APAP. In fasted mice, the oral administration of APAP produced serious liver injury, while it was not the case in the fed mice. As the antibody production was measured under these conditions, APAP significantly depressed the antibody production in fed mice as well as in fasted mice. The rate of B220 positive cells in the splenocytes was significantly decreased by APAP administration in both the fasted and fed mice. Splenocytes proliferative responses following mitogenic stimulation with concanavalin A or lipopolysaccharide were inhibited by APAP. Moreover, APAP added directly to the splenocyte culture also inhibited the in vitro antibody-producing response to SRBC. These findings indicate that the APAP-induced depression of antibody production may not be a secondary response to APAP-hepatitis, but may be a primary response to APAP.
Notes
Toxicology
Regular Articles
  • Orish Ebere Orisakwe, Onyenmechi Johnson Afonne, Chudi Emma Dioka, Pat ...
    原稿種別: Regular Article
    専門分野: Toxicology
    2002 年 25 巻 2 号 p. 206-208
    発行日: 2002年
    公開日: 2002/04/27
    ジャーナル フリー
    Rinbacin is a local Nigerian herbal remedy. The effects of rinbacin on testicular histology were studied in prepubertal rats. Sexually immature male rats, divided into seven per group, were given rinbacin in drinking waters at 0, 26.25 g/l, or 52.50 g/l for 13 weeks, after which the animals were killed and testes excised, weighed, and processed for histologic study. The epididymal sperm number (ESN) was determined. There were no significant effects of either the low or high doses of rinbacin on fluid intake, body weight, testicular weight, and testis-body weight ratio. There was, however, a significant (p<0.05) decrease in the ESN of animals at both doses of rinbacin. Histologic examination of the testes indicated that the high dose of rinbacin induced significant degenerative changes, while the low dose had only a mild effect on testicular histology. Rinbacin decreases the ESN and causes degenerative lesions, especially at the high dose, in prepubertal rats.
  • Kiyomatsu Hashizume, Jo Nanya, Chitose Toda, Teruyo Yasui, Hideo Nagan ...
    原稿種別: Regular Article
    専門分野: Toxicology
    2002 年 25 巻 2 号 p. 209-214
    発行日: 2002年
    公開日: 2002/04/27
    ジャーナル フリー
    Phthalate esters (PEs), especially di-n-butyl phthalate (DBP) and di-(2-ethylhexyl) phthalate (DEHP) were detected in various water samples such as river water, well water and tap water. On degradation tests of PEs, Tempaku River water degraded almost 100% of diethyl phthalate (DEP), di-isobutyl phthalate and DBP, and approximately 70% of DEHP. All eight isolates from Tempaku River water (R1—R7, D1) did not degrade dimethyl phthalate (DMP), but showed biodegrading ability for the other PEs. The DBP-degrading ability was particularly high for the isolates R1—R3 and D1 of Acinetobacter lwoffii. Crude enzyme solutions prepared from bacterial cells of these isolates showed a higher degrading activity for DEHP compared with that for microbially-degradable DBP. Particularly high DEHP-degrading activity was found for crude enzyme solutions of the isolate D1. As metabolites from the river water and bacterial isolates, DMP and an unknown diester were produced from DEP. DMP, DEP, monomethyl phthalate, monobutyl phthalate (MBP) and an unknown diester were produced from DBP. DBP, DEP, DMP and an unknown diester were produced from DEHP. As metabolites by the crude enzyme solutions, DMP, MBP and an unknown diester derivative were produced from DBP. DBP, mono-(2-ethylhexyl) phthalate and an unknown diester derivative were produced from DEHP. Diesters with shortened alkyl carbon chains were also found as metabolites by the isolates and their crude enzyme solutions. The results suggest that the alkyl chains in the diesters are also decomposed in addition to monoester formation from DBP or DEHP at the first step reported for animals and some types of bacteria.
Medical Chemistry
Regular Articles
  • Joseph Thomas Leonard, Navaneetharaman Anbalagan, Shanmugam Sadish Kum ...
    原稿種別: Regular Article
    専門分野: Medical Chemistry
    2002 年 25 巻 2 号 p. 215-217
    発行日: 2002年
    公開日: 2002/04/27
    ジャーナル フリー
    In the present study, a series of 2-(3′-substituted-2′-hydroxypropylamino)pyridines were synthesized and characterized by IR, 1H-NMR and elemental analysis. The compounds were investigated for anticonvulsant (150, 300 mg/kg) and cardiac activity. 2-(3′-Diethylamino-2′-hydroxypropylamino)pyridine 3 was found to exhibit the highest anticonvulsant activity. 2-(3′-Dimethylamino-2′-hydroxypropylamino)pyridine 2 and 2-[3′-(4″-nitrophenyl-amino)-2′-hydroxypropylamino]pyridine 6 were found to exhibit negative ionotropic activity. 2-(3′-Dimethylamino-2′-hydroxypropylamino)pyridine 2, 2-[3′-(4″-nitrophenylamino)-2′-hydroxypropylamino]pyridine 6 and 2-(3′-piperidino-2′-hydroxypropylamino)pyridine 8 were found to antagonize exhibit β-adrenergic activity.
Pharmacognosy
Regular Articles
  • Nobuyoshi Tomari, Yasuhiro Ishizuka, Akira Moriya, Satoru Kojima, Take ...
    原稿種別: Regular Article
    専門分野: Pharmacognosy
    2002 年 25 巻 2 号 p. 218-222
    発行日: 2002年
    公開日: 2002/04/27
    ジャーナル フリー
    The phylogenetic relationship of Cistanche deserticola, C. salsa and C. tubulosa was analyzed by comparing the nucleotide sequences of the plastid rps2 gene and the intergenic spacer region between rpl16 and rpl14. By comparison of sequence data, the Cistanche samples were distinguishable from each other. The results were consistent with their anatomical and chemical characteristics. Intraspecific variations were found in C. salsa and C. tubulosa among the geographical populations. The NJ tree reconstructed based on the sequence data revealed that C. deserticola and C. salsa from China were closely related to each other, and C. tubulosa was placed as an outgroup of them.
  • Motoh Mutsuga, Keisuke Kojima, Miwako Yamashita, Takamasa Ohno, Yukio ...
    原稿種別: Regular Article
    専門分野: Pharmacognosy
    2002 年 25 巻 2 号 p. 223-228
    発行日: 2002年
    公開日: 2002/04/27
    ジャーナル フリー
    Pancratistatin derivatives, 1-O-(3-hydroxybutyryl)pancratistatin (HBP) and 1-O-(3-O-β-d-glucopyranosylbutyryl)pancratistatin (GBP), showed strong cytostatic activity against rat embryo fibroblast 3Y1 at concentrations less than 1 µM. When the effect on cell cycle progression was examined in 3Y1 fibroblasts arrested at G0/G1 phase by serum deprivation, HBP, GBP, and pancratistatin inhibited the progression of 3Y1 fibroblasts from G0/G1 to S phase. In addition, when the effect on cell cycle progression was studied in 3Y1 fibroblasts synchronized at late G1/early S phases by treating with hydroxyurea, HBP blocked further progression through S phase, while GBP and pancratistatin did not affect the progression, but retarded it. On the other hand, when the effect of HBP and GBP on the progression was evaluated in promyelocytic leukemia HL-60RG cells synchronized at G0/G1 phase, the cells did not progress into S phase and accumulated in sub G0/G1 phase, which indicated apoptotic cells. These findings suggest that of Amaryllidaceae alkaloids, HBP blocks the progression of cell cycle at least at G0/G1 and S phases and GBP does at least at G0/G1 phase, resulting in apoptosis induction in tumor cells.
Notes
Biopharmacy
Regular Articles
  • Akemi Kobayashi, Akira Hachiya, Atsushi Ohuchi, Takashi Kitahara, Yosh ...
    原稿種別: Regular Article
    専門分野: Biopharmacy
    2002 年 25 巻 2 号 p. 229-234
    発行日: 2002年
    公開日: 2002/04/27
    ジャーナル フリー
    It is known that expression of endothelin-1 (ET-1) increases in the epidermis after UVB irradiation, and that this plays an important role during the induction of pigmentation both as a mitogen and as a melanogen for normal human melanocytes (NHMC). When ET-1 acts on NHMC via the endothelin B receptor (ETBR) on their cell surface, mobilization of intracellular calcium is induced, which is followed by activation of Raf-1 located upstream of mitogen activated protein kinase (MAPK). We have continued the search for new agent which inhibit this calcium mobilization and we have found that an extract of Althaea officinalis L. has such an action. In this study, we investigated the precise inhibitory mechanism of this botanical extract on the ET-1-induced activation of melanocytes. Treatment of NHMC with this extract abrogated the stimulatory effect of ET-1 on proliferation and also on activation of MAPK in the intracellular signal transduction pathway, but did not affect the binding of ET-1 to the ETBR or the production of Inositol 1,4,5-Trisphosphate (IP3). Further, when this extract was used to treat normal human keratinocytes (NHKC), secretion of ET-1 by those cells was reduced. Taken together, these findings indicate that an extract of A. officinalis inhibits both the secretion of ET-1 from NHKC and the action of ET-1 on NHMC mainly by suppressing the ET-1-induced calcium mobilization without the modification of IP3 production, which in turn suggests that this extract is a useful ingredient for a whitening agent.
Notes
  • Kenji Tokui, Yoshitaka Asai, Toshiharu Arakawa, Takatoshi Matsumoto, T ...
    原稿種別: Note
    専門分野: Biopharmacy
    2002 年 25 巻 2 号 p. 264-267
    発行日: 2002年
    公開日: 2002/04/27
    ジャーナル フリー
    Salazosulfapyridine (SASP) is widely used orally and rectally in the treatment of ulcerative colitis. SASP is mainly metabolized by hydrolysis and the main active metabolite, 5-aminosalicylic acid (5-ASA), has an antiinflammatory effect. In the present study, we prepared suppositories containing 6.5 mmol of SASP and an enema containing 6.5 mmol of 5-ASA. We measured the concentrations of SASP and its various metabolites, 5-ASA, sulfapyridine (SP), acetylated metabolite of SP (Ac-SP), and N-acetyl-5-ASA (Ac-5-ASA), in the serum and urine after a single administration of each preparation to healthy male volunteers. When the SASP suppository was administered, the maximum concentration (Cmax) of SASP and Ac-5-ASA was 2.5±0.4 and 0.5±0.2 µM and the time to Cmax (Tmax) was 5 and 12 h, respectively. The Cmax value of SP, which causes side effects, was one-half of that of the parent compound. No 5-ASA in the serum was observed. When the 5-ASA enema was administered, Cmax and Tmax values of 5-ASA and Ac-5-ASA were 5.8±2.0 and 13.3±3.6 µM and 1 and 7 h, respectively. The area under the serum concentration–time curve (AUC) of SASP was 27.4±4.8 µM·h, a finding similar to that of 5-ASA after the administration of the 5-ASA enema (29.4±11.1 µM·h). The percentage of urinary recovery of SASP 24 h after administration of the SASP suppository was approximately 0.2%. These results indicate that SASP administered rectally is almost completely hydrolyzed in the colon and that 5-ASA is partially absorbed from the small intestine in unchanged form. On the other hand, approximately 0.3% of 5-ASA was recovered in the urine in unchanged form after the administration of the 5-ASA enema, whereas the urinary recovery of Ac-5-ASA was more than 10%. The present findings suggest that 5-ASA has favorable absorptive properties and can be expected to have systemic action after rectal administration of a 5-ASA enema.
  • Kyoko Kofuji, Tomohiro Ito, Yoshifumi Murata, Susumu Kawashima
    原稿種別: Note
    専門分野: Biopharmacy
    2002 年 25 巻 2 号 p. 268-271
    発行日: 2002年
    公開日: 2002/04/27
    ジャーナル フリー
    Chitosan (CS) gel beads were prepared in 10% amino acid solution (pH 9) and modified by forming an electrostatic complex between the amino group of CS and the carboxyl group of chondroitin sulfate (Cho). Modification of the CS gel matrix by Cho inhibited the in vitro release of prednisolone (PS) from the gel beads. CS gel beads modified by Cho (CS-Cho) were implanted into air pouches (AP) prepared subcutaneously on the dorsal surfaces of mice. No inflammatory response was observed. The in vivo release of PS from CS-Cho gel beads and their biodegradation in the AP was slower than beads without Cho treatment. After 28 days of implantation, CS-Cho gel beads (deacetylation of CS: 90%) were still detectable, although they had become softer and smaller. Modification of the CS gel matrix by Cho controls the biodegradation of the beads and the release of the drug. This effect makes these beads a promising biocompatible and biodegradable vehicle for sustained drug delivery.
Communication to the Editor
  • Yoshiaki Amakura, Tomoaki Tsutsumi, Masafumi Nakamura, Hiroko Kitagawa ...
    原稿種別: Communication
    専門分野: [not specified]
    2002 年 25 巻 2 号 p. 272-274
    発行日: 2002年
    公開日: 2002/04/27
    ジャーナル フリー
    A preliminary screening for the inhibitory effects on the activation of the aryl hydrocarbon receptor (AhR) by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) by applying AhR-based bioassays for dioxins, the Ah-Immunoassay and CALUX assay, was attempted. Thirty-nine food extracts including vegetables, fruits, herbs, and teas were initially screened in vitro. We first examined the application of both bioassay methods using green tea extracts and (−)-epigallocatechin gallate, reported antagonists of the AhR, since the results could reveal an inhibitory effect versus the control in both assays. Food extracts were then tested. Among the herbs, extracts of sage, among the vegetables, green leafy ones such as spinach, and among the fruit, citrus showed inhibitory effects on AhR activation by TCDD, although some tested samples did not show parallel behavior in both assays. Sage had a remarkable inhibitory effect (79% in the CALUX assay and 83% in the Ah-Immunoassay compared with control) and its effects were dose dependent. The results suggest that these assays might be applicable to the preliminary screening of antagonist activity against the AhR. Moreover, based on these results, the potential benefit of factors that function as dietary ligands of the AhR and are present in several foodstuffs is indicated.
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