Journal of Pharmacological Sciences
Online ISSN : 1347-8648
Print ISSN : 1347-8613
ISSN-L : 1347-8613
Volume 98 , Issue 4
Showing 1-18 articles out of 18 articles from the selected issue
Current Perspective: New Technique
  • Ikunobu Muramatsu, Takashi Tanaka, Fumiko Suzuki, Zhang Li, Yasuko Hir ...
    2005 Volume 98 Issue 4 Pages 331-339
    Published: 2005
    Released: August 20, 2005
    [Advance publication] Released: August 05, 2005
    JOURNALS FREE ACCESS
    The radioligand binding assay technique is an extremely powerful tool for studying receptors. It allows an analysis of the interactions of hormones, neurotransmitters, and related drugs with their receptors. Most of the binding assays have widely been applied to crude membrane fractions prepared from many tissues, but in the conventional method, there are some limitations such as a yield loss of receptor-bearing membranes and a change in receptor environment upon homogenization and fractionation. Recently, in order to overcome these problems, a binding assay has been developed using intact tissue segments. This article presents a brief overview of the tissue segment binding assay that has been developed mainly in our department. Practical guidelines for setting up this new assay are presented, including segment preparation, choice of appropriate radioligand, optimizing assay conditions, and appropriate methods for data analysis. The unique advantages and disadvantages of the tissue segment binding method are discussed in comparison with those of conventional membrane binding methods. We suggest that the tissue segment binding method is a powerful tool for detecting the native properties of receptors occurring in tissues and cells without altering their environment.
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Critical Review
  • Sherifa A. Hamed, Toshitaka Nabeshima
    2005 Volume 98 Issue 4 Pages 340-353
    Published: 2005
    Released: August 20, 2005
    [Advance publication] Released: August 02, 2005
    JOURNALS FREE ACCESS
    Neurologists have little concern about the high atherosclerotic risk among epileptics. Recent evidences mount that chronic epilepsy and prolonged use of antiepileptic drugs (AEDs) are associated with multiple risk factors that are critically implicated in pathobiology and dysfunction of the vessel wall through complex molecular mechanisms that promote atherogenesis. This review is concerned with three metabolic alterations, which are attributed as major risk factors for atherosclerosis among epileptics: altered metabolism of a) homocysteine (Hcy), b) lipids and lipoproteins, and c) uric acid. Most conventional AEDs reduce folic acid levels, thereby raising Hcy levels. Hyperhomosysteinemia is recently believed to induce endothelial dysfunction and promote atherosclerosis through complex oxidative and excitatory neurotoxic molecular mechanisms. However, Hcy itself is a convulsing substance with increased seizure recurrence and intractability to antiepileptic medications. AEDs can disturb lipid metabolism with resultant hypercholestrolemia and dyslipidemia, common recognized risks for atherosclerosis. Altered uric acid metabolism is common among epileptics. Uric acid has been implicated in endothelial cell damage and decreased endothelial nitric oxide bioavailability. In the presence of atherosclerotic milieu, uric acid interacts with other substrate toxicities and increased reactive oxygen species, accelerating atherosclerosis. The above information forms the rationale for future routine screening and correction of such metabolic alterations in epileptics. A convincing argument now develops that routine polyvitamin supplementation (folic acid, vitamin B12, vitamin B6, vitamin C, vitamin E, and β-carotene) becomes increasingly important for women and men receiving AEDs at all ages. The atheroprotective effect of multivitamins is through their antioxidant and anti-inflammatory effects together with their lipid and Hcy lowering effects.
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Full Papers
  • Rajan Ravindran, Rathinasamy Sheela Devi, James Samson, Manohar Senthi ...
    2005 Volume 98 Issue 4 Pages 354-360
    Published: 2005
    Released: August 20, 2005
    JOURNALS FREE ACCESS
    In this modern world, stress and pollution are unavoidable phenomena affecting the body system at various levels. A large number of people are exposed to potentially hazardous noise levels in daily modern life, such as noise from work environments, urban traffic, and household appliances. A variety of studies have suggested an association between noise exposure and the occurrence of disorders involving extra-auditory organs such as disorders of the nervous, endocrine, and cardiovascular systems. In this study, Wistar strain albino rats were subjected to 100 dB broadband white noise, 4 h daily for 15 days. The high-pressure liquid chromatographic estimation of norepinephrine, epinephrine, dopamine, and serotonin in discrete regions of the rat brain indicates that noise stress can alter the brain biogenic amines after 15 days of stress exposure. Ocimum sanctum (OS), a medicinal herb that is widely claimed to posses antistressor activity and used extensively in the Indian system of medicine for a variety of disorders, was chosen for this study. Administration of the 70% ethanolic extract of OS had a normalizing action on discrete regions of brain and controlled the alteration in neurotransmitter levels due to noise stress, emphasizing the antistressor potential of this plant.
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  • Yan-Qiu Liu, Song You, Shin-ichi Tashiro, Satoshi Onodera, Takashi Ike ...
    2005 Volume 98 Issue 4 Pages 361-371
    Published: 2005
    Released: August 20, 2005
    [Advance publication] Released: July 29, 2005
    JOURNALS FREE ACCESS
    Our previous study showed that oridonin isolated from Rabdosia rubescens enhanced phagocytosis of apoptotic cells by macrophage-like U937 cells through tumor necrosis factor (TNF) α and interleukin (IL)-1β release. In this study, we further investigated signaling events involved in oridonin-augmented phagocytosis. Phagocytic stimulation was significantly suppressed by inhibitors, including a phosphoinositide 3-kinases (PI3K) inhibitor (wortmannin), a protein kinase C (PKC) inhibitor (stauroporine), and a phospholipase C (PLC) inhibitor (U73122). Exposure of U937 cells to oridonin caused an increase in PKC activity time- dependently, which was prevented by pretreatment with inhibitors of PI3K and PLC. Simultaneously, the activation of protein kinase B (PKB/Akt) and the increased expression of PLCγ2 were also blocked by wortmannin. In addition, an extracellular signal-regulated kinase (ERK) MAPK inhibitor, PD98059, suppressed oridonin-augmented phagocytosis, whereas the p38 MAPK inhibitor (SB203580) and c-Jun N-terminal kinase (JNK) MAPK inhibitor (SP98059) had no inhibitory effect. Furthermore, pretreatment of U937 cells with anti-TNFα and anti-IL-1β antibodies blocked oridonin-induced phagocytic stimulation as well as phosphorylation of ERK, but did not block the activation of PKC, indicating that these signaling events are triggered by oridonin, whereas secreted TNFα or IL-1β only activate the ERK-dependent pathway. Taken together, oridonin is suggested to enhance phagocytosis of apoptotic bodies by activating PI3K, PKC, and ERK-dependent pathways.
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  • Ryotaro Wake, Shokei Kim-Mitsuyama, Yasukatsu Izumi, Kaoru Yoshida, Ya ...
    2005 Volume 98 Issue 4 Pages 372-379
    Published: 2005
    Released: August 20, 2005
    [Advance publication] Released: July 29, 2005
    JOURNALS FREE ACCESS
    In this study, we examined whether an angiotensin II type 1 (AT1)-receptor blocker improves diastolic heart failure (DHF) in Dahl salt-sensitive (DS) rats. DHF was prepared by feeding DS rats on 8% NaCl diet from 7 weeks of age. DHF was estimated with echocardiography by measuring E velocity / A velocity (E/A) of left ventricular inflow. DS rats with established DHF were orally given candesartan (1 mg/kg per day) or vehicle. After 13 days of treatment, candesartan significantly improved DHF, as shown by the reduction of E/A from 4.49 ± 1.04 to 1.98 ± 0.54 (P<0.05) and prolonged survival rate more than the vehicle. Cardiac fibrosis, apoptosis, and gene expression were estimated by Sirius Red-staining, TUNEL-staining, and Northern blot analysis, respectively. The improvement of DHF by candesartan was accompanied by the decrease in cardiac hypertrophy, fibrosis, and apoptosis, and the reduction of gene expression of brain natriuretic peptide, collagen I, and monocyte chemoattractant protein-1. Moreover, candesartan decreased cardiac inflammatory cells and reactive oxygen species, estimated by counting ED-1-positive cells and the measurement of 4-hydroxy-2-nonenal staining, respectively. These results indicate that candesartan can improve diastolic dysfunction and may slow the progression of cardiac remodelling in DS rats with established DHF.
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  • Takeshi Nabe, Kayoko Kubota, Tetsuya Terada, Hiroshi Takenaka, Shigeka ...
    2005 Volume 98 Issue 4 Pages 380-387
    Published: 2005
    Released: August 20, 2005
    [Advance publication] Released: August 02, 2005
    JOURNALS FREE ACCESS
    We previously reported that when Japanese cedar pollen was prophylactically p.o. administered before a sensitization stage in a guinea-pig model of allergic rhinitis, pollen-induced nasal blockage was suppressed. In this study, we evaluated whether the oral immunotherapy is also effective when the pollen extract was administered starting from the day when the nasal blockage was clearly induced and whether the effectiveness continued after cessation of the immunotherapy. Sensitized animals were repeatedly challenged by pollen inhalation once every week. After the 7th challenge, the extract was orally administered twice a week until the 30th challenge. At the 11th challenge, the oral immunotherapy showed inhibition of the biphasic nasal blockage. The effectiveness was consistently observed during the immunotherapy until the 30th challenge. Furthermore, the increased nasal responsiveness to intranasal application of leukotriene D4 was markedly suppressed by the immunotherapy. Interestingly, even after cessation of the therapy, inhibition of the nasal blockage was sustained for more than 2 months. Nevertheless, neither sneezing nor antigen-specific IgE antibody production was substantially influenced by the immunotherapy. In conclusion, Oral immunotherapy may be clinically useful for allergic nasal blockage. Mechanisms underlying the effectiveness may be associated with the hyporesponsiveness of the nasal mucosa to released mediators.
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  • Masayuki Uchida, Noriko Endo, Kimiko Shimizu
    2005 Volume 98 Issue 4 Pages 388-395
    Published: 2005
    Released: August 20, 2005
    [Advance publication] Released: August 05, 2005
    JOURNALS FREE ACCESS
    The 13C-breath test has been used to clinically evaluate gastric emptying. However, this method has not been sufficiently validated in experimental animals. The present study aimed to establish a simple and noninvasive 13C-breath-test system in Sprague-Dawley male rats. After fasting, rats were orally administered Racol containing 13C-acetic acid and housed in a desiccator. The expired air in the chamber was collected in a breath-sampling bag using a tube and aspiration pump. The level of 13CO2 in the expired air was measured using an infrared spectrometer at appropriate intervals for 120 min. During this period, the rate of 13CO2 excretion increased, peaked, and decreased thereafter. The maximum concentration (Cmax) and area under the curve (AUC120 min) of 13CO2 excretion increased in volume- and dose-dependent manners. The time taken to reach the maximum concentration (Tmax) of 13CO2 excretion increased as the volume increased, but was not affected by the dose of 13C-labeled acetic acid. Metoclopramide dose-dependently increased the Cmax and shortened Tmax of 13CO2 excretion compared with those of the control rats, whereas the AUC120 min was not affected. These results confirm that this simple method can successfully evaluate gastric emptying. Moreover, this system is suitable for investigating additional physiological functions using other labeled compounds.
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  • Hiroe Nakayama, Hisashi Yamakuni, Mika Higaki, Hirofumi Ishikawa, Kats ...
    2005 Volume 98 Issue 4 Pages 396-403
    Published: 2005
    Released: August 20, 2005
    [Advance publication] Released: July 29, 2005
    JOURNALS FREE ACCESS
    We investigated the effect of FK1052 [(+)-8,9-dihydro-10-methyl-7-[(5-methyl-1H-imidazol-4-yl)methyl]pyrido[1,2-a]indol-6(7H)-one hydrochloride], a 5-HT3- and 5-HT4-receptor antagonist, on the emesis induced by motion stimuli, copper sulfate, or cisplatin in either Suncus murinus or ferrets and also clarified the role of the 5-HT3 and 5-HT4 receptors in these models. In Suncus murinus, oral administration of FK1052 (100 μg/kg) completely prevented emesis induced by cisplatin (18 mg/kg, i.p.). Intraperitoneal injection of scopolamine (10 mg/kg) and promethazine (32 mg/kg), but not FK1052 (1 mg/kg), significantly reduced the emetic responses by motion stimuli. In ferrets, copper sulfate (40 mg/kg, p.o.)-induced emesis was moderately prevented by FK1052 (3.2 mg/kg), but not by granisetron (3.2 mg/kg). Cisplatin-induced acute (10 mg/kg, i.v.) and delayed (5 mg/kg, i.p.) emesis were significantly reduced by single and multiple intravenous injection of both FK1052 (3.2 mg/kg) and granisetron (3.2 mg/kg), respectively. The present study suggests that FK1052 may be useful against both acute and delayed emesis induced by cancer chemotherapy. Moreover, it is suggested that blockades of 5-HT3 and 5-HT4 receptors are not relevant to the control of motion sickness; and furthermore, it suggested that blocking 5-HT4 receptors in addition to 5-HT3 receptors does not have an additional effect on the control of cisplatin-induced emesis, but that 5-HT4 receptors are at least partly involved in the mechanism of emesis induced by copper sulfate.
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  • Chikaomi Yamada, YiXue Xue, Daisuke Chino, Keitaro Hashimoto
    2005 Volume 98 Issue 4 Pages 404-410
    Published: 2005
    Released: August 20, 2005
    [Advance publication] Released: July 29, 2005
    JOURNALS FREE ACCESS
    We investigated the effects of KB-R9032 (N-(4-isopropyl-2,2-dimethyl-3-oxo-3,4-dihydro-2H-benzo[1,4]oxazine-6-carbonyl) guanidine methanesulfonate), a new Na+/H+ exchange inhibitor, on a coronary artery occlusion/reperfusion-induced arrhythmia model in pentobarbital anesthetized dogs. KB-R9032 reduced the number of ventricular premature contractions seen during the coronary occlusion, while it did not alter the heart rate, mean blood pressure, or electrocardiographic parameters (PR, QRS, or QTc interval). KB-R9032 also decreased the incidence of fatal ventricular fibrillation during coronary artery occlusion and/or after reperfusion. These antiarrhythmic effects were observed not only in the pre-ischemic administration group, but also in the group given KB-R9032 at the 15th min of the 30-min occlusion. These findings support the view that Na+/H+ exchanger may play an important role in inducing coronary ischemia/reperfusion arrhythmias. This suggests that the use of Na+/H+ exchange inhibitors, such as KB-R9032, may be an effective clinical approach to suppress sudden cardiac death due to acute myocardial ischemia/reperfusion such as during coronary bypass surgery, cardiac valve surgery, or percutaneous transluminal coronary angioplasty.
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  • Shiho Okano, Hideaki Nagaya, Nobuhiro Inatomi
    2005 Volume 98 Issue 4 Pages 411-418
    Published: 2005
    Released: August 20, 2005
    [Advance publication] Released: July 29, 2005
    JOURNALS FREE ACCESS
    Stress-induced colonic functional changes have been investigated mainly under conditions involving physical stress, like in the restraint stress model. In this study, we established a new stress-induced defecation model involving the placement of Mongolian gerbils in a novel environment (novelty stress) and determined the effects of several drugs on novelty stress-induced fecal pellet output. When animals kept in groups were placed individually in small cages, the fecal pellet output markedly increased, although the upper intestinal transit measured by charcoal method was not changed. The concentration of plasma adrenocorticotropic hormone was moderately but significantly increased by the novelty stress. Drugs reportedly effective for stress-induced defecation, like alosetron hydrochloride, atropine sulfate, and trimebutine maleate, inhibited both the novelty stress-induced increase in fecal pellet output and spontaneous defecation. In contrast, TAK-637, a tachykinin NK1-receptor antagonist, and diazepam inhibited the novelty stress induced defecation but did not inhibit spontaneous defecation. The present study indicated that novelty stress increases fecal pellet output without affecting the upper intestinal transit; this model may be useful for evaluating the effects of drugs on stress-stimulated colonic motility.
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  • Miki Kishitake, Korehito Yamanouchi
    2005 Volume 98 Issue 4 Pages 419-424
    Published: 2005
    Released: August 20, 2005
    [Advance publication] Released: August 02, 2005
    JOURNALS FREE ACCESS
    The inhibitory effects of 8-OH-DPAT, a 5-HT1A-receptor agonist, and baclofen, a GABAB-receptor agonist, on lordosis were examined in estrogen and progesterone-treated ovariectomized rats with lesions in either the dorsal raphe nucleus (DRN) or septum and in rats with either sham lesions or no lesions. The first behavior test series was carried out 6 days after implantation of the rats with silicon tubes containing estradiol. Four hours after injection with 0.5 mg progesterone, behavioral tests were performed before and 30 min after an injection with 1 mg/kg body weight 8-OH-DPAT. As a result, the mean lordosis quotient (LQ)s were changed from 100 to less than 20 before and after the injection in all groups. These results suggest that 8-OH-DPAT acts on areas other than the DRN and the septum, leading to a decrease in lordosis. Two weeks after implantation with estradiol, the next behavioral test series was carried out after injection with progesterone. Behavioral tests were performed before and after an injection with 10 mg baclofen. The results showed that the mean LQs decreased after the injection in all groups, but the mean LQ in the DRN lesion group was higher than that in the sham groups. These results indicate that baclofen may act partially on the DRN in inhibiting lordosis in female rats.
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  • Satoshi Amano, Tomohisa Ishikawa, Koichi Nakayama
    2005 Volume 98 Issue 4 Pages 425-429
    Published: 2005
    Released: August 20, 2005
    [Advance publication] Released: August 02, 2005
    JOURNALS FREE ACCESS
    Blood vessels are receptive to hemodynamic forces, such as blood pressure and flow, which result in myogenic responses. The present study aimed to investigate the effect of mechanical stresses on L-type voltage-dependent Ca2+ channels in rabbit cerebral artery myocytes. Cell swelling induced by the exposure to a 16% hypotonic solution increased peak values of whole-cell Ba2+ currents (IBa). Similarly, an elevation of bath perfusion rate increased peak values of IBa. However, the response was reduced by the continued fluid flow stimulation and the current amplitude almost returned to the baseline. This reduction of the current was abolished by pretreatment with thapsigargin, implying the contribution of Ca2+ release from the sarcoplasmic reticulum to the response. These results suggest that L-type Ca2+ currents are facilitated not only by cell swelling but also by fluid flow in cerebral artery myocytes.
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  • Yasushi Hirota, Mikie Suzuki, Nobuo Katsube
    2005 Volume 98 Issue 4 Pages 430-438
    Published: 2005
    Released: August 20, 2005
    [Advance publication] Released: August 02, 2005
    JOURNALS FREE ACCESS
    Neutrophil elastase (NE) is a factor that aggravates colitis. We investigated the influence of thromboxane A2 (TXA2) and leukotriene B4 (LTB4) on NE release in Syrian hamsters with trinitrobenzene sulfonic acid-induced colitis. Colonic specimens with colitis were incubated with U-46619 (a TXA2 analogue) or LTB4 in vitro and NE release was examined. As a result, U-46619 increased NE release, while LTB4 had no effect. The NE release induced by U-46619 was inhibited by a TP-receptor antagonist. To demonstrate that TXA2 caused NE release in vivo as well, while LTB4 did not, colitis animals were treated with nordihydroguaiaretic acid (NDGA), a dual inhibitor of cyclooxygenase/lipoxygenase; and colonic luminal TXB(A)2 and LTB4 levels and NE activity were determined. The TXB(A)2 level was significantly correlated with NE activity, while no correlation was found between LTB4 and NE activity. An inhibitory effect of NDGA on the ulcer area was also observed, and NE activity was significantly correlated with the ulcer area. The suppression of TXA2 production by NDGA may result in the inhibition of NE release so that colonic tissue damage becomes less severe. Regulation of NE release is a new biological action of TXA2 that has not been reported before.
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  • Jung-Woo Park, Hui-Yul Roh, In-Sang Jung, Yeo-Pyo Yun, Kyu-Yang Yi, Su ...
    2005 Volume 98 Issue 4 Pages 439-449
    Published: 2005
    Released: August 20, 2005
    [Advance publication] Released: August 05, 2005
    JOURNALS FREE ACCESS
    The cardioprotective effects of the novel sodium/hydrogen exchanger-1 (NHE-1) inhibitor KR-32560 {[5-(2-methoxy-5-fluorophenyl)furan-2-ylcarbonyl]guanidine} were studied in an anesthetized rat model of 30-min ischemia / 2.5-h reperfusion heart injury. KR-32560 (0.01 - 1 μM) dose-dependently inhibited NHE-1-mediated rabbit platelet swelling induced by intracellular acidification. KR-32560 at 0.1 and 1.0 mg/kg (i.v. bolus, given 10 min before ischemia) reduced infarct size from 65.9% (control) to 49.7% and 32.7%, respectively, while reducing the extension of myocardial injury (mm3/g of left heart weight) from 405.1 (control) to 302.9 and 185.4, respectively (all P<0.05 vs control). KR-32560 dose-dependently reduced the total number of ventricular premature beats (VPBs) during ischemia from 510.2 (control) to 353.8 and 134.2 beats (all P<0.05, n = 6), while reducing ventricular tachycardia (VT) incidence from 49.3 (control) to 26.8 and 4.3 and VT duration from 249.2 s (control) to 150.5 and 26.7 s (all P<0.05, n = 6). KR-32560 dose-dependently reduced ventricular fibrillation (VF) incidence from 19.0 (control) to 9.2 and 1.2 and VF duration from 88.0 s to 34.5 and 2.8 s (all P<0.05, n = 6). KR-32560 also exerted similar effects on reperfusion arrhythmias, except for VPBs. These results indicate that KR-32560 may exert significant cardioprotective effects in ischemia/reperfusion heart injury.
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  • Masanori Yoshii, Atsushi Jikuhara, Shuji Mori, Hiromi Iwagaki, Hideo K ...
    2005 Volume 98 Issue 4 Pages 450-458
    Published: 2005
    Released: August 20, 2005
    [Advance publication] Released: August 10, 2005
    JOURNALS FREE ACCESS
    We found that striptease-positive mast cells were abundant in the invasive front of human colon adenocarcinoma by examining 30 cases. Because tryptase has been suggested to be the agonist proteinase for protease-activated receptor-2 (PAR-2), we investigated the effects of stimulation of PAR-2 by tryptase on the cell signaling and proliferation of DLD-1, a human colon carcinoma cell line. PAR-2 stimulation by tryptase induced the increase in [Ca2+]i, which was desensitized by the prior application of PAR-2 activating peptide (AP). The proliferative responses of DLD-1 to tryptase and PAR-2 AP were associated with the phosphorylation of MEK and MAP kinase. Inhibition of MEK by PD98059 completely inhibited the proliferation-enhancing effects of tryptase and PAR-2 AP as well as phosphorylation of MAP kinase. Moreover, tryptase and PAR-2 AP stimulated the production of prostaglandin E2 and the inhibition of prostaglandin synthesis by indomethacin or NS398 resulted in the complete inhibition of the proliferative responses to tryptase and PAR-2 AP. Furthermore, the tryptase-stimulated proliferation of DLD-1 was concentration-dependently inhibited by nafamostat mesilate, a specific inhibitor of tryptase. These results as a whole indicated that tryptase has proliferative effects on DLD-1 through cyclooxygenase- and MAP kinase-dependent manners acting on PAR-2 by its proteolytic activity.
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Short Communications
  • Mi-Hyeon Jang, Myoung-Hwa Lee, Hong Kim, Sam-Jun Lee, Young-Je Sim, Ch ...
    2005 Volume 98 Issue 4 Pages 459-462
    Published: 2005
    Released: August 20, 2005
    [Advance publication] Released: August 05, 2005
    JOURNALS FREE ACCESS
    Maternal alcohol consumption during pregnancy can produce teratogenic effects and has a detrimental effect on the development of the fetus. In this study, the dose-dependent effect of maternal alcohol administration on the expression of nitric oxide synthase (NOS) in the hippocampus of the offspring rats was investigated. From the present result, it was shown that expression of NOS is decreased following treatment with maternal alcohol in a dose-dependent fashion. The present results suggest that suppression of NOS expression in the hippocampus of offspring rats with maternal alcohol mediates the associated developmental retardation and/or anomalies.
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  • Goutarou Katsuno, Hideo K. Takahashi, Hiromi Iwagaki, Kenji Mizuno, Sh ...
    2005 Volume 98 Issue 4 Pages 463-466
    Published: 2005
    Released: August 20, 2005
    [Advance publication] Released: August 10, 2005
    JOURNALS FREE ACCESS
    Little has been reported on the drugs inducing production of monocyte-derived cytokines like interleukin (IL)-18 and IL-12. We found that nafamostat mesilate elicits IL-12, IL-18, tumor necrosis factor-α and interferon-γ production, and the expression of intercellular adhesion molecules-1, B7.1, B7.2, CD40, and CD40 ligand in human peripheral blood mononuclear cells. The cytokine production and adhesion molecule expression were abolished by anti-IL-12 and IL-18 antibodies. Therefore, IL-18 and IL-12 may play roles in the significant and immediate effects of nafamostat mesilate.
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  • Monrudee Sukma, Michihisa Tohda, Hiroshi Watanabe, Kinzo Matsumoto
    2005 Volume 98 Issue 4 Pages 467-470
    Published: 2005
    Released: August 20, 2005
    [Advance publication] Released: August 05, 2005
    JOURNALS FREE ACCESS
    The alteration of the editing pattern of serotonin 2C receptor (5-HT2CR) mRNA has been reported during cell differentiation. Since editing of 5-HT2CR mRNA is regulated by adenosine deaminases acting on RNA (ADARs), it is of interest to investigate if the expression of these enzymes changes during cell differentiation. The level of ADAR1 mRNA in NG108-15 cells was decreased by cell differentiation. These results suggest that the decrease of ADAR1 expression during cell differentiation may play an important role in the differentiation-induced alteration of the 5-HT2CR editing pattern in NG108-15.
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