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REFERENCE LINKING PLATFORM OF KOREA S&T JOURNALS
> Journal Vol & Issue
Biomolecules & Therapeutics
Journal Basic Information
Journal DOI :
The Korean Society of Applied Pharmacology
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Volume & Issues
Volume 15, Issue 4 - Dec 2007
Volume 15, Issue 3 - Sep 2007
Volume 15, Issue 2 - Jun 2007
Volume 15, Issue 1 - Mar 2007
Selecting the target year
Progress in the Direct Application of Pharmacogenomics to Patient Care: Sustaining innovation
Frueh, Felix W. ; Lesko, Lawrence J. ; Burckart, Gilbert J. ;
Biomolecules & Therapeutics, volume 15, issue 1, 2007, Pages 1~6
DOI : 10.4062/biomolther.2007.15.1.001
The application of the knowledge from the Human Genome Project to clinical medicine will be through both industrial drug development and the application of pharmacogenomics (PG) to patient care. The slow uptake of clinical innovations into clinical practice can be frustrating, but understanding the history of acceptance and sustaining medical innovation is critically important to position PG to succeed. This primarily means that PG tests must have legitimacy; they must be thoroughly validated, must be cost-effective, must be widely accepted by medical practitioners, must be supported by public policy, and must have a way of being easily incorporated into current medical practice. They must also lead to actionalble decisions by health care providers for their patients. Innovative PG assays should be tested in the best US laboratories, and reimbursement for testing must be accepted at the federal and state level. The companies providing these PG tests should be capable of sup-porting the interpretation and use of the test throughout medical practice. Advances such as the addition of PG information to drug labeling and the routine use of validated biomarkers to determine choice of cancer chemotherapy have been made. The PG research community must pay attention to the principles that have been previously described for acceptance and sustaining medical innovations in order for PG to be widely accepted in clinical medical practice.
Molecular Events on Experimental Skin Inflammation and Modulation by Topical Anti-inflammatory Flavonoids
Kim, Hyun-Pyo ;
Biomolecules & Therapeutics, volume 15, issue 1, 2007, Pages 7~15
DOI : 10.4062/biomolther.2007.15.1.007
There have been various animal models of skin inflammation. These models have been used for establishing anti-inflammatory activity of the topical agents including cosmetics. Here, the molecular mechanisms of most widely-used animal models of skin inflammation including contact irritation, acute and chronic inflammation, and delayed-type hypersensitivity are summarized. Against these animal models, varieties of plant flavonoids showed anti-inflammatory activity. The action mechanisms of anti-inflammation by topical flavonoids are presented. A therapeutic potential of flavonoids is discussed.
Beyond Clot Dissolution; Role of Tissue Plasminogen Activator in Central Nervous System
Kim, Ji-Woon ; Lee, Soon-Young ; Joo, So-Hyun ; Song, Mi-Ryoung ; Shin, Chan-Young ;
Biomolecules & Therapeutics, volume 15, issue 1, 2007, Pages 16~26
DOI : 10.4062/biomolther.2007.15.1.016
Tissue plasminogen activator (tPA) is a serine protease catalyzing the proteolytic conversion of plasminogen into plasmin, which is involved in thrombolysis. During last two decades, the role of tPA in brain physiology and pathology has been extensively investigated. tPA is expressed in brain regions such as cortex, hippocampus, amygdala and cerebellum, and major neural cell types such as neuron, astrocyte, microglia and endothelial cells express tPA in basal status. After strong neural stimulation such as seizure, tPA behaves as an immediate early gene increasing the expression level within an hour. Neural activity and/or postsynaptic stimulation increased the release of tPA from axonal terminal and presumably from dendritic compartment. Neuronal tPA regulates plastic changes in neuronal function and structure mediating key neurologic processes such as visual cortex plasticity, seizure spreading, cerebellar motor learning, long term potentiation and addictive or withdrawal behavior after morphine discontinuance. In addition to these physiological roles, tPA mediates excitotoxicity leading to the neurodegeneration in several pathological conditions including ischemic stroke. Increasing amount of evidence also suggest the role of tPA in neurodegenerative diseases such as Alzheimer`s disease and multiple sclerosis even though beneficial effects was also reported in case of Alzheimer`s disease based on the observation of tPA-induced degradation of
aggregates. Target proteins of tPA action include extracellular matrix protein laminin, proteoglycans and NMDA receptor. In addition, several receptors (or binding partners) for tPA has been reported such as low-density lipoprotein receptor-related protein (LRP) and annexin II, even though intracellular signaling mechanism underlying tPA action is not clear yet. Interestingly, the action of tPA comprises both proteolytic and non-proteolytic mechanism. In case of microglial activation, tPA showed non-proteolytic cytokine-like function. The search for exact target proteins and receptor molecules for tPA along with the identification of the mechanism regulating tPA expression and release in the nervous system will enable us to better understand several key neurological processes like teaming and memory as well as to obtain therapeutic tools against neurodegenerative diseases.
Anxiolytic and Antidepressant Activities of Ginsenoside Rb1
Choi, Jong-Hyun ; Yoon, Seo-Young ; Choi, Eun-Joo ; Ryu, Yim-Seon ; Ko, Hong-Sook ; Yim, Dong-Sool ; Her, Youl ; Lee, Yong-Soo ; Song, Mi-Ryoung ; Cheong, Jae-Hoon ;
Biomolecules & Therapeutics, volume 15, issue 1, 2007, Pages 27~33
DOI : 10.4062/biomolther.2007.15.1.027
The psychopharmacological profile of ginsenosides has not yet been confirmed systematically although various neuropharmacological activities associated with them have been investigated. In the present study, the psychological activities of Rb1 were investigated to evaluate whether it can be used in treatment or prevention of psychological disorders. Rb1 was intravenously injected at doses of O.2,2,5 and 10 mg/kg. The effects of Rb1 on the
ion influx were investigated using IMR-32 human neuroblastoma cells. Moreover, locomotor activity, forced swimming activity, activity on rotating rod and activity in elevated plus-maze were tested in mice. Rb1 increased the
influx into the intracell region in a dose-dependent manner. Rb1 did not cause change in behavior in total open field when locomotor activity was tested, however it increased activities, especially, such as rearing frequency in center area. Administration of Rb1 at 0.2 mg/kg significantly reduced activities on rotating rod however administration at high dosages had no effect on them. Rb1 administration decreased animal immobile time in a water chamber in a dose dependent manner, and increased the strong mobile time of animals. In conclusion, the present results demonstrate that Rb1 contributes to the psychopharmacological effects of ginseng and may be used in treatment or prevention of psychological disorders such as anxiety or depression.
Increase of Amyloid-Beta Peptide Generation in High Cholesterol Diet Rabbit Brain
Lee, Yong-Kyoung ; Son, Dong-Ju ; Lee, Jae-Woong ; Lee, Hyung-Woo ; Yun, Young-Won ; Oh, Ki-Wan ; Hong, Jin-Tae ;
Biomolecules & Therapeutics, volume 15, issue 1, 2007, Pages 34~39
DOI : 10.4062/biomolther.2007.15.1.034
Alzheimer`s disease (AD) is an abnormal accumulation of the
in specific brain region. It has been speculated that disturbance in cholesterol homeostasis may contribute to the etiology of AD by increasing
generation. However, conclusive evidence and possible mechanism has not been reported. In the present study, we demonstrated that rabbits treated with 0.5% cholesterol for 16 weeks increased serum total cholesterol, triacylglycerol, and low-density lipoprotein levels.
levels is higher in the hippocampus of brain in cholesterol dieted rabbits than that of normal diet rabbis. Expression and activities of
secretases, the enzymes that cleave
-amyloid precursor protein to generate
, were also increased in hippocampus of high cholesterol dieted rabbit than those of normal dieted rabbits. Our results suggest that high cholesterol diet may be associated with increased
accumulation in the brain of rabbits, and suggest that high cholesterol diet may be causal factor in the development or progression of AD.
Antihypertensive Effects of Enantiomers of Amlodipine Camsylate, a Novel Salt of Amlodipine
Oh, Kwang-Seok ; Kim, Maeng-Sup ; Lee, Byung-Ho ;
Biomolecules & Therapeutics, volume 15, issue 1, 2007, Pages 40~45
DOI : 10.4062/biomolther.2007.15.1.040
The vascular relaxant effects on isolated rat aorta of amlodipine camsylates (S-, R-enantiomer, and R/S-racemate), were evaluated and compared with that of S-amlodipine besylate. Furthermore, antihypertensive effects were measured in spontaneously hypertensive rat (SHR). The S-amlodipine camsylate concentration-dependently inhibited
-induced contraction of rat aorta with a very slow onset of action (reached its maximum at 3.5h;
nM), having a potency 2-fold higher than those of R/S-amlodipine camsylate
and similar to those of S-amlodipine besylate
, whereas the R-amlodipine camsylate has 590-fold lower vasorelaxant activity
. In SHR, orally administered S-amlodipine camsylate produced a dose-dependent and long-lasting (>>10 h) antihypertensive effect
, with a potency 2-fold higher than those of R/S-amlodipine camsylate
and similar to those of S-amlodipine besylate
. In contrast, the R-amlodipine camsylate has no effect even-though administrated high concentration 10 mg/kg. These results suggest that S-amlodipine camsylate has the potency and long-lasting antihypertensive activity as single enantiomer drug, and its antihypertensive effect is not significantly different to that of S-amlodipine besylate.
Isolation and Antioxidative Activities of Caffeoylquinic Acid Derivatives and Flavonoid Glycosides from Leaves of Sweet Potato (Ipomoea batatas L.)
Kim, Hyoung-Ja ; Jin, Chang-Bae ; Lee, Yong-Sup ;
Biomolecules & Therapeutics, volume 15, issue 1, 2007, Pages 46~51
DOI : 10.4062/biomolther.2007.15.1.046
Bioassay-directed chromatographic fractionation of an ethyl acetate extract from leaves of sweet potato (Ipomoea batatas L.) afforded six quinic acid derivatives: 3,5-epi-dicaffeoylquinic acid (1), 3,5-dicaffeoylquinic acid (2), methyl 3,5-O-dicaffeoylquinate (3), methyl 3,4-dicaffeoylquinate (4), methyl 4,5-dicaffeoylquinic acid (5),4,5-dicaffeoylquinate (6), and two phenolic compounds: caffeic acid (7) and caffeic acid methyl ester (8) together with three flavonoids: quercetin 3-O-
-D-glucopyranoside (9), quercetin 3-O-
-D-glucopyranoside, isoquercitrin (10) and kaempferol 3-O-
-D-glucopyranoside (11). The structures of these compounds were elucidated by the aid of spectroscopic methods. These compounds were assessed for antioxidant activities using three different cell-free bioassay systems. All isolates except 11 showed potent DPPH and superoxide anion radicals scavenging, and lipid peroxidation inhibitory activities. 3,5-epi-DCQA (1) and methyl quinates (3-5) along with flavonoide 9 were isolated for the first time from this plant.
Effects of Proton on Lysolipid-induced Actions in OGR1-subfamily GPCRs
Lim, Sung-Mee ; Im, Dong-Soon ;
Biomolecules & Therapeutics, volume 15, issue 1, 2007, Pages 52~57
DOI : 10.4062/biomolther.2007.15.1.052
Lysolipids such as lysophosphatidylcholine (LPC), sphingosylphosphorylcholine (S PC), galactosylsphingosine (psychosine) have been matched as ligands for OGR1-subfamily G-protein-coupled receptors (GPCR), consisted of OGR1, GPR4, G2A, and TDAG8. Recently, those members of GPCRS have been reported as proton-sensing GPCRs. We used Jurkat T cells, which express four members of OGR1 subfamily GPCRs endogenously to investigate effects of proton on lysolipid-induced several cellular events. We found no significant effect of proton on the lysolipid-induced
increase and ROS production in Jurkat T cells. Further investigation is necessary to clarify the relationship of lysolipid and proton on the OGR1-subfamily GPCRs.
Extremely Low Frequency Magnetic Field is an Environmental Stress Factor by Exerting Oxidative Stress
Park, Yong-Jin ; Park, Won-Joo ; Yim, Sung-Hyuk ; Yang, Seong-Jun ; Sun, Yuan Lu ; Jeong, Ji-Hoon ; Park, Eon-Sub ;
Biomolecules & Therapeutics, volume 15, issue 1, 2007, Pages 58~64
DOI : 10.4062/biomolther.2007.15.1.058
The previous study reported the biological effect of magnetic field exerted by acting on endocrine and anti-oxidant system. The present study aims to study whether ELF-MF (extremely low frequency magnetic field) affects the physiological endocrine systems such as thyroid and whether ELF-MF affects the defense system against oxidative stress when it alters the function of thyroid. Finally, we correlate the effects of MF on oxidative stress, and adrenal and thyroid with an environmental stress factor. We exposed sham or MF to rats for 5 or 25 days. After the exposure, we determined pain sensitivity, level of TSH,
in plasma. We also assayed in whole brain, lipid peroxidation, the activity of enzymatic anti-oxidant defense including superoxide dismutase(SOD) and glutathione peroxidase (GPx), and non enzymatic defense such as reduced or oxidized glutathione contents. MF induced the hypersensitivity to thermal stimuli with the reduction of latency.
levels were also increased by the exposure of MF. In addition, we observed the rise of MDA level in rat brain by MF although the MF did not change superoxide dismutase and glutathione peroxidase activity. The effect of MF on both reduced and oxidized glutathione results in decrease in reduced or oxidized glutathione in whole brain. In every experiment, there was no significant difference in MF influence between short term (5 days) and long term (25 days) exposure. Taken together, MF exposure affects the thyroid hormonal control in brain. The elevated thyroid hormone acts on brain, leading to hyper-utilization of oxygen. This phenomenon may be correlated with oxidative stress resulting from MF exposure. In conclusion, we suggest that MF exposure may be an environmental stress by exerting oxidative stress.
Elimination of Saturated Fatty Acids, Toxic Cyclic nonapeptide and Cyanogen Glycoside Components from Flax Seed Oil
Choi, Eun-Mi ; Kim, Jeung-Won ; Pyo, Mi-Kyung ; Jo, Sung-Jun ; Han, Byung-Hoon ;
Biomolecules & Therapeutics, volume 15, issue 1, 2007, Pages 65~72
DOI : 10.4062/biomolther.2007.15.1.065
Flax seed(Linseed, Linum usitatissimum L.) and its oil, a richest source of alpha-linolenic acid(ALA)(
), contain saturated fatty acids, neurotoxic cyanogen glycosides and immuno-suppressive cyclic-nonapeptides. Present paper describes the development of two chemical processes, Process-A and -B, to remove saturated fatty acids and to destroy cyclic nonapeptides and cyanogen glycosides from flax seed oil. Process-A consists of three major steps, i.e., extraction of fatty acid mixture by alkaline saponification, removal of saturated fatty acid by urea-complexation, and triglyceride reconstruction of unsaturated fatty acid via fatty acyl-chloride activation using oxalyl chloride. Process-B consists of preparation of fatty acid ethyl ester by transesterification, elimination of saturated fatty acid ester by urea-complexation, and reconstruction of triglyceride by interesterification with glycerol-triacetate (triacetin). The destruction of lipophilic cyclic nonapeptide during saponification or transesterification processes could be demonstrated indirectly by the disappearance of antibacterial activity of bacitracin, an analogous cyclic-decapeptide. The cyanogen glycosides were found only in the dregs after hexane extraction, but not in the flax seed oil. The reconstructed triglyceride of flax seed oil, obtained by these two different pathways after elimination of saturated fatty acid and toxic components, showed agreeable properties as edible oil in terms of taste, acid value, iodine and peroxide value, glycerine content, and antioxidant activity.