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Volume 115, Issue 7
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Naoto OKU1995 Volume 115 Issue 7 Pages 483-498
Published: July 25, 1995
Released on J-STAGE: May 30, 2008
JOURNAL FREE ACCESSLiposomes are the models of biomembranes and are new thought to be ideal tools in the field of drug delivery system. Liposomalization of various drugs has been revealed to enhance their efficacy and to reduce the side effect of the drugs. For the site-specific delivery, intracellular targeting, and controlled release of drugs, many functional liposomes have been developed based on their natures as the models of biomembranes. In this report, the preparation and characterization of functional liposomes are discussed. At first, the hydration process of lipids which is an important step for the liposomal preparation was discussed. Secondly, three kinds of functional liposomes were presented, namely, thermosensitive liposomes for delivering macromolecules, pH-sensitive liposomes for the cytosolic delivery of encapsulated materials, and reticuloendothelial system (RES)-avoiding liposomes for the passive targeting to tumor tissues. Finally, the actual usefulness of RES-avoiding liposomes modified with a uronic acid derivative, palmityl-D-glucuronide for the tumor imaging and therapy was demonstrated.View full abstractDownload PDF (1508K) -
Toshitaka NABESHIMA1995 Volume 115 Issue 7 Pages 499-512
Published: July 25, 1995
Released on J-STAGE: May 30, 2008
JOURNAL FREE ACCESSNerve growth factor (NGF) plays an important role in the survival and maintenance of cholinergic neurons in the central nervous system. In senile dementia of the Alzheimer type (SDAT), learning and memory are impaired by the loss of neurons in the magnocellular cholinergic neuronal system. It is, therefore, of interest to investigate the role of NGF in this degenerative disorder. Since NGF does not cross the blood-brain barrier and is easily metabolized by peptidases when administered peripherally, it can be used for medical treatment only when directly injected into the brain. We tried to develop drugs which could be taken orally and stimulate the NGF synthesis in the brain. In addition, we attempted to develop a SDAT animal model using osmotic minipump to infuse β-amyloid protein into cerebral ventricle, since there are no SDAT model animals accompanied with various pathophysiological changes. We demonstrate here that the oral administration of propentofylline, idebenone and trimethylquinone derivative, potent in vitro NGF synthesis stimulators, induced the increase in NGF protein and mRNA, and in choline acetyltransferase activity, in basal forebrain-lesioned and aged rats. but not in intact young rats. These drugs also ameliorated the behavioral deficits in habituation, water maze, and passive avoidance tasks in these animals. These results suggest that these drugs stimulated NGF synthesis in vivo and ameliorated the behavioral deficits which were accompanied with the reduced choline acetyltransferase activity in the basal forebrain-lesioned and aged rats. In terms of the SDAT animal model, the performance of the water maze and passive avoidance tasks was impaired and choline acetyltransferase activity significantly decreased in β-amyloid protein-treated rats. Histochemical results showed the deposition of β-amyloid protein in the cortex and hippocampus and atrophy and loss of hippocampal neurons. These results suggest that the deposition of β-amyloid protein in the brain is related to the impairment of learning and cholinergic neuronal degeneration, and that β-amyloid protein-treated rats could be an animal model for SADT and used for the screening of drugs for SDAT.View full abstractDownload PDF (1772K) -
Takashi TSURUO1995 Volume 115 Issue 7 Pages 513-522
Published: July 25, 1995
Released on J-STAGE: May 30, 2008
JOURNAL FREE ACCESSResistance of tumors to a variety of chemotherapeutic agents presents a major problem in cancer treatment. The gene responsible for multidrug resistance, termed mdrl, encodes a membrane glycoprotein (P-glycoprotein) that acts as a pump to transport various cytotoxic agents. The P-glycoprotein has been shown to bind anticancer drugs and several resistance-reversing agents including calcium channel blockers, and to be an ATPase. The P-glycoprotein was found to function in the blood-brain barrier. The physiological function of the P-glycoprotein in relation to therapy is discussed.View full abstractDownload PDF (1255K) -
Shunji ISHIWATA, Kunihiko ITOH, Takahumi YAMAGUCHI, Shiro SASAKI, Naka ...1995 Volume 115 Issue 7 Pages 523-527
Published: July 25, 1995
Released on J-STAGE: May 30, 2008
JOURNAL FREE ACCESSIt is known that in cancer patients elevated levels of modified nucleosides originated from RNA are excreted in the urine. Modified nucleosides in the serum are thought to be more useful than those in the urine as tumor markers because they are not influenced by other factors. However the determination of these nucleosides is difficult because of their low amounts. To examine the efficacy of the modified nucleosides in the serum as tumor markers, ascites and solid tumor mouse models were prepared, and the amounts of 1-methyladenosine and pseudouridine in the serum were determined. Along with the growth of ascites tumor, the amounts of 1-methyladenosine and pseudouridine in the serum increased. The modified nucleosides in the serum in a solid tumor model also increased. This is the first report on the variation in the amount of 1-methyladenosine in the serum of tumor models, and the results suggest the usefulness of measuring the amounts of 1-methyladenosine and pseudouridine in the serum as tumor markers.View full abstractDownload PDF (523K) -
Terumi UEMURA, Yuko M. SAGESAKA, Naoto OKU, Shoji OKADA1995 Volume 115 Issue 7 Pages 528-536
Published: July 25, 1995
Released on J-STAGE: May 30, 2008
JOURNAL FREE ACCESSThe effect of saponins on the one of major functions of neutrophil, namely the generation of superoxide anion (O2-), was investigated using retinoic acid (RA)-differentiated HL-60 cells (promyelocytic leukemia cells). The generation of O2- from the cells induced by saponins was monitored by the reduction of cytochrome c. All five species of crude saponins studied here, i.e. tea-leaf saponins, tea-seed saponins, ginsenosides, soyasaponins and saikosaponins, stimulated the generation of O2- from RA-differentiated HL-60 cells. Tea-leaf saponins showed the highest stimulating activity, followed by soyasaponins and ginsenosides. The cytotoxic activity of saponins was determined by the dye exclusion method after the incubation of RA-differentiated HL-60 cells with various concentrations of saponins. Saikosaponins and tea-seed saponins exhibited considerable cytotoxic activity and hemolytic activity. To examine the involvement of protein kinase C (PKC) in the neutrophil activation by saponins, the effect of H-7, an antagonist of PKC, on the generation of O2- induced by saponins was investigated. H-7 was found to inhibit the generation of O2- in a dose-dependent manner, suggesting the participation of PKC in the neutrophil stimulating process by saponins. Tea-leaf saponins, ginsenosides and soyasaponins, which had high neutrophil stimulating activity and low cytotoxic activity, seemed to be useful as a biological response modifier (BRM) for the activation of neutrophil.View full abstractDownload PDF (825K) -
Sumiyuki AKIHAMA, Yosifumi MATSUDA, Tohru FUKASE, Aiko YAMANAKA, Masay ...1995 Volume 115 Issue 7 Pages 537-542
Published: July 25, 1995
Released on J-STAGE: May 30, 2008
JOURNAL FREE ACCESSIn order to estimate the effects of sialic acid residues in fibrinogen on the fibrinogen-fibrin conversion by bovine thrombin the Michaelis constant (Km) and maximum velosity (Vmax) were determined. The Km value obtained by the use of intact-fibrinogen was smaller than that of asialo-fibrinogen. This fact suggests that the sialic acid residues affected the formation of the enzyme-substrate complex. It was also found that in comparison with the asialo-fibrinogen, the intactfibrinogen was significantly influenced in the gel formation time by the ionic strength in the reaction solution.View full abstractDownload PDF (558K) -
Osami TAKEDA, Eiji MIKI, Susumu TERABAYASHI, Minoru OKADA, Ye LU, HuiS ...1995 Volume 115 Issue 7 Pages 543-552
Published: July 25, 1995
Released on J-STAGE: May 30, 2008
JOURNAL FREE ACCESSIn a previous paper, we reported the variation of essential oil components comtained in a rhizome of Atractylodes lancea that is a botanical origin of Chinese crude drug"Cangzhu( ?? ?? )."In this paper, A. chinensis, an another botanical origin of this drug, was investigated in the same manner. The plant (179 individuals) growing wild was collected in Hebei, Shangdong and the North of Jiangsu provinces, China at flowering time. A. koreana that has been an origin of the drug was also obtained at the Shangdong peninsula. Six essential oil components, that is elemol (1), atractylon (2), hinesol (3), β-eudesmol (4), selina-4 (14), 7 (11)-dien-8-one (5) and atractylodin (6) contained in their rhizomes were determined with GC. Two types were recognized for a species A. chinensis according to the statistical analysis of essential oil components. One type is characterized by containing 3 and 4 as main components, and the plants belonging to this type are distributed in the North of the Huang-He river. Another type is characterized by containing 2 or 6 as main components, and the plants belonging to this type are distributed in the South of this river. Deposition of a white cotton like crystal was not observed from examined the plants. Compound 2 was detected in all the populations of A. chinensis including A. koreana. Especially, 6 was contained in all examined the plants. These results were compared with those of A. lancea.View full abstractDownload PDF (954K)
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