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Volume 87 (2001)
- Issue 4 Pages 245-
- Issue 3 Pages 171-
- Issue 2 Pages 97-
- Issue 1 Pages 1-
Volume 87, Issue 2
Displaying 1-11 of 11 articles from this issue
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Reviews
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William M. PardridgeSubject area: Infomation Science
2001 Volume 87 Issue 2 Pages 97-103
Published: 2001
Released on J-STAGE: November 05, 2001
JOURNAL FREE ACCESSBrain drug targeting technology is based on the application of four gene technologies that enable the delivery of drugs or genes across the blood-brain barrier (BBB) in vivo. I) Genetic engineering is used to produce humanized monoclonal antibodies that target endogenous BBB transporters and act as vectors for delivery of drugs or genes to the human brain. The conjugate of a neurotherapeutic and a BBB transport vector is called a chimeric peptide. Epidermal growth factor chimeric peptides have been used for neuroimaging of brain cancer. Brain-derived neutrophic factor chimeric peptides have marked neuroprotective effects in brain stroke models. II) Imaging gene expression in the brain in vivo is possible with sequence-specific antisense radiopharmaceuticals, which are conjugated to BBB drug targeting vectors. III) Brain gene targeting technology enables widespread expression of an exogenous gene throughout the central nervous system following an intravenous injection of a non-viral therapeutic gene. IV) A BBB genomics program enables the future discovery of novel transport systems expressed at the BBB. These transporters may be carrier-mediated transport systems, active efflux transporters, or receptor-mediated transcytosis systems. The future discovery of novel BBB transport systems and the application of brain drug targeting technology will enable the delivery to the brain of virtually any neurotherapeutic, including small molecules, large molecules and gene medicines.View full abstractDownload PDF (448K) -
Akira Yoshida, Hiroshi UedaSubject area: Infomation Science
2001 Volume 87 Issue 2 Pages 104-109
Published: 2001
Released on J-STAGE: November 05, 2001
JOURNAL FREE ACCESSLysophosphatidic acid (LPA, 1-acyl-sn-glycerol-3-phosphate) is a well-known lipid growth factor that is found widely in various tissues including brain and is reported to drive different intracellular signaling pathways. In the nervous system, LPA studies have drawn many neuroscientists’ attention because it has some actions related to neurogenesis such as cell rounding and proliferation. Remarkable advances in this field have been obtained along with the discovery of the cDNA clone for its receptor, vzg1/edg2, a member of the seven transmembrane-type edg family. Successive studies have revealed that edg2 activation by LPA mediates several neurobiological actions related to neurogenesis, neuronal excitability and survival activity on developing and postnatal neurons. Here we focused their molecular basis of signaling through G proteins and in vivo roles of edg2 in such neurobiological events.View full abstractDownload PDF (234K)
Full Papers
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Fumihiro Ohara, Nobuhiro Yamamoto, Kazuhiro Maeda, Toru Ozaki, Jiro Se ...Subject area: Infomation Science
2001 Volume 87 Issue 2 Pages 110-116
Published: 2001
Released on J-STAGE: November 05, 2001
JOURNAL FREE ACCESSInhibition of Na+/H+ exchanger has been reported to protect hearts from ischemia and reperfusion injury. However, the effect of Na+/H+ exchange inhibition on hypothermic ischemic injury has not been extensively studied and the results are inconsistent. The purpose of this study was to investigate whether inhibition of Na+/H+ exchange with FR183998 (5-(2,5-dichlorothiphen-3-yl)-3-[(2-dimethylaminoethyl)carbamoyl]benzoylguanidine dihydrochloride), a potent Na+/H+ exchange inhibitor, would show protective effects against postischemic cardiac dysfunction after hypothermic as well as normothermic ischemia and furthermore, after hypothermic cardioplegic arrest in isolated rat hearts. FR183998 (3.2 × 10−8 – 3.2 × 10−7 M) improved post-ischemic recovery of left ventricular developed pressure and suppressed the increase of left ventricular end diastolic pressure in a dose-dependent manner, after not only 45 min of normothermic ischemia but also 6 h of hypothermic ischemia. Furthermore, FR183998 (10−7 – 10 −6 M) significantly reduced creatine kinase release during reperfusion after 3 h of hypothermic ischemia with cardioplegia. These results indicate that FR183998 has a potent protective effect on postischemic cardiac dysfunction after normothermic and hypothermic ischemia, and also on reperfusion injury after hypothermic cardioplegic arrest, suggesting that its effect would be additive to cardioplegia.View full abstractDownload PDF (243K) -
Masahito Watanabe, Hisako Yamagishi-Wang, Mitsuru KawaguchiSubject area: Infomation Science
2001 Volume 87 Issue 2 Pages 117-124
Published: 2001
Released on J-STAGE: November 05, 2001
JOURNAL FREE ACCESSWe investigated the responses of salivary secretion and the susceptibility of the muscarinic receptors in the salivary glands of the streptozotocin (STZ)-induced diabetic rats (STZ rats). Giving water ad libitum, the amount of whole saliva with no stimulation was similar in the STZ and the control rats. Pilocarpine increased salivary secretion in both groups, although the effect in the STZ rats was two to three fold less than in the control rats. If the animals were restricted from taking water for 6 h, salivary secretion was not slightly changed in the STZ rats in spite of a remarkable increase in the control. An obvious decrease in salivary secretion of the STZ rats was negatively correlated with an increase in urination. Furthermore, salivary secretion from the parotid gland was increased in a dose-dependent manner with pilocarpine in the control rats, but not in the STZ rats. In the [3H]quinuclidinyl benzilate (QNB) binding studies for muscarinic receptor of the STZ rats, Bmax was decreased in the parotid gland and Kd was increased in the submandibular gland. Competitive inhibition of [3H]QNB binding to both glands showed an increase in IC50 of pilocarpine and carbachol. These results suggest that a decrease in salivary secretion of STZ rats is not only induced by a water loss, but also closely associated with the lowered susceptibility of the muscarinic receptors.View full abstractDownload PDF (926K) -
SeungSoo Chung, SeongChun Kwon, YunSuk Kim, DuckSun Ahn, YoungHo Lee, ...Subject area: Infomation Science
2001 Volume 87 Issue 2 Pages 125-133
Published: 2001
Released on J-STAGE: November 05, 2001
JOURNAL FREE ACCESSEffects of clonidine, an imidazoline derivative as well as α2-adrenoceptor agonist, on carbachol (CCh)-evoked contraction in guinea pig ileal smooth muscle were studied using isometric tension recording. To investigate the cellular mechanisms of the inhibitory effect of clonidine, its effects on CCh-evoked nonselective cationic current (ICCh), voltage-dependent Ca2+ current (ICa) and voltage-dependent K+ current (IK) was also studied using patch-clamp recording techniques in single ileal cells. Clonidine inhibited the contraction evoked by CCh (1 μM) in a concentration-dependent manner with an IC50 valve of 61.7 ± 2.5 μM. High K+ (40 mM)-evoked contraction was only slightly inhibited even when clonidine was used at 300 μM. Externally applied clonidine inhibited ICCh dose-dependently with an IC50 of 42.0 ± 2.6 μM. When applied internally via patch pipettes, clonidine was without effect. An ICCh-like current induced by GTPγS was also inhibited by bath application of clonidine. None of KU14R and BU224, both imidazoline receptor blockers, and yohimbine, an α2-adrenergic blocker, significantly affects the inhibitory effect of clonidine on ICCh. Clonidine (300 μM) only slightly decreased membrane currents flowing through voltage-gated Ca2+ channels or K+ channels. These data indicate that clonidine relaxes smooth muscle contraction produced by muscarinic receptor activation and suggest that the effect of clonidine seems due mainly to inhibition of ICCh via acting directly on the involved cationic channel.View full abstractDownload PDF (299K) -
Role of Adenosine in Renal Protection Induced by a Brief Episode of Ischemic Preconditioning in RatsHaruko Sugino, Hideyo Shimada, Kanji TsuchimotoSubject area: Infomation Science
2001 Volume 87 Issue 2 Pages 134-142
Published: 2001
Released on J-STAGE: November 05, 2001
JOURNAL FREE ACCESSThe protective effect of a brief episode of ischemic preconditioning was examined at an early phase of ischemic-reperfusion injury in the rat kidney. Rats were subjected to 50 min of left renal artery occlusion followed by 120 min of reperfusion. Ischemic preconditioned rats were subjected to preconditioning with two cycles of 3-min ischemia and 5-min reperfusion (IPC). Ischemic-reperfusion injury led to a low recovery of the glomerular filtration rate (GFR). Overt morphological changes, consisting of blood trapping and tubular collapse, were seen. IPC improved the recovery of GFR and renal morphology. The IPC effect was not blocked by 8-(p-sulfophenyl)-theophylline (SPT), a non-selective adenosine receptor antagonist, by 1,3-dipropyl-8-cyclopentylxanthine (DPCPX), a selective A1-receptor antagonist, or by 3,7-dimethyl-1-propargylxanthine (DMPX), a selective A2-receptor antagonist. Intravenous infusion of adenosine (30 μg/min per rat, for 5 min) prior to the 50-min occlusion improved the recovery of GFR, and this protection of GFR was blocked by SPT. Thus, both IPC and exogenous adenosine attenuated ischemic-reperfusion injury of the kidney. However, because three adenosine receptor antagonists failed to abolish the protective effect of IPC, there is no evidence to indicate that activation of adenosine receptors contributes to the IPC effect in the kidney.View full abstractDownload PDF (577K) -
Motohisa Suzuki, Mayumi Suzuki, Kazunori Sato, Sekiko Dohi, Takashi Sa ...Subject area: Infomation Science
2001 Volume 87 Issue 2 Pages 143-150
Published: 2001
Released on J-STAGE: November 05, 2001
JOURNAL FREE ACCESSAlthough improving energy metabolism in ischemic brain has been accepted for the treatment of cerebrovascular diseases, administration of glucose, as an energy substrate, would aggravate ischemic brain damage via activating anaerobic glycolysis, which leads to lactate accumulation. β-hydroxybutyrate (BHB) is one of the ketone bodies that can be utilized as an energy source during starvation. The purpose of our study was to define the protective effects of BHB on brain damage induced by hypoxia, anoxia and ischemia. The isotonic solution of BHB administered 30 min before the induction of ischemia at doses over 50 mg · k g −1 · h −1 showed remarkable protective effects against hypoxia and anoxia. BHB administered immediately after a bilateral carotid artery ligation at a dose of 30 mg · kg−1 · h −1 significantly suppressed the elevation of cerebral water and sodium contents as well as maintaining high ATP and low lactate levels. In contrast, glycerin, a hypertonic agent, substantially reduced the water content but did not show any significant effect on other parameters. We demonstrated that BHB, unlike glycerin, when used as an energy substrate in ischemic brain, has protective effects on cerebral hypoxia, anoxia and ischemia-induced metabolic change.View full abstractDownload PDF (614K) -
Shuichi Yotsuya, Hiroshi Shikama, Masashi ImamuraSubject area: Infomation Science
2001 Volume 87 Issue 2 Pages 151-157
Published: 2001
Released on J-STAGE: November 05, 2001
JOURNAL FREE ACCESSWe examined the therapeutic effects of the inflammatory cell infiltration inhibitor IS-741 (N-(2-((ethylsulfonyl)amino)-5-(trifluoromethyl)-3-pyridinyl)-cyclohexanecarboxamide monosodium salt monohydrate) on a rat colitis model. As a result of its effects on leukocyte infiltration, IS-741 inhibits cell adhesion, alleviates symptoms and signs of pancreatitis and multiple organ failure and demonstrates a life-saving effect in a model of severe acute pancreatitis. A rat model was prepared by inducing colitis with 3% dextran sodium sulfate (DSS) and maintaining pathology with 1% DSS. Repeated oral administration of IS-741 at 1, 10 or 100 mg/kg per day was conducted for 2 weeks (during treatment with 1% DSS). IS-741 at each dose decreased the area of erosion in the large intestine, thickening of the wall of the large intestine and anemia caused by melena. Some effects of IS-741 were nearly equivalent to those of the control compound salazosulfapyridine. Furthermore, IS-741 markedly alleviated inflammatory cell infiltration into the intestinal wall. IS-741 improved lesions in a rat DSS model by inhibiting leukocyte infiltration, suggesting the possibility of clinical application of this drug for IBD.View full abstractDownload PDF (769K) -
Yasuro Kataoka, Hidehisa Masui, Nobuo Iwata, Ichiro WakabayashiSubject area: Infomation Science
2001 Volume 87 Issue 2 Pages 158-163
Published: 2001
Released on J-STAGE: November 05, 2001
JOURNAL FREE ACCESSThe effects of extracellular acidosis on gallbladder contraction were investigated using gallbladder strips isolated from guinea pigs. In an acidic medium (pH 6.9), gallbladder contraction induced by histamine and prostaglandin E2 was significantly lower than that in a normal medium (pH 7.4). Acidosis affected neither gallbladder contraction induced by histamine in the absence of extracellular Ca2+ nor that induced by KCl. Acidosis significantly inhibited Ca2+-induced contraction in the presence of sodium fluoride and phorbol 12,13-dibutyrate but not that in the presence of KCl. Staurosporine (30 nM) significantly inhibited gallbladder contraction induced by histamine and prostaglandin E2, but not that by KCl. Histamine-induced contraction in the presence of staurosporine was not affected by acidosis. Acidosis significantly inhibited Ca2+-induced contraction in the presence of histamine but not that in the presence of both histamine and staurosporine. These results suggest that extracellular acidosis selectively inhibits gallbladder contraction mediated by protein kinase C activation.View full abstractDownload PDF (232K)
Short Communications
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Ernani Luís Rhoden, Luiz Pereira-Lima, Cláudio Telö ...Subject area: Infomation Science
2001 Volume 87 Issue 2 Pages 164-166
Published: 2001
Released on J-STAGE: November 05, 2001
JOURNAL FREE ACCESSWe evaluated the effects of α-tocopherol (vitamin E) on the products of lipid peroxidation and serum creatinine levels in a rat model of renal ischemia-reperfusion. The animals were submitted to sham operation or renal ischemia-reperfusion, and they were pretreated with α-tocopherol or the vehicle saline. In four groups, we analyzed the lipid peroxidation products by measuring malondialdehyde and chemiluminescence levels. In the other three groups, we studied the serum creatinine levels after the procedures. In our study, the pretreatment with α-tocopherol reduced significantly the lipid peroxidation of renal cells and renal dysfunction induced by renal ischemia-reperfusion in rats.View full abstractDownload PDF (81K) -
Ken-ichi Hayashi, Toshihiko Kaise, Kenji Ohmori, Akio Ishii, Akira Kar ...Subject area: Infomation Science
2001 Volume 87 Issue 2 Pages 167-170
Published: 2001
Released on J-STAGE: November 05, 2001
JOURNAL FREE ACCESSIntradermal injections of poly-L -arginine induce cutaneous vascular hyperpermeability and scratching behavior in rats. Recently, we elucidated that the plasma extravasation involved both histamine and substance P, while the scratching behavior involved substance P, but not histamine. This study examined the effects of olopatadine hydrochloride (olopatadine), an antiallergic drug with histamine H1-antagonistic action, on the poly-L -arginine-induced responses. Olopatadine (1 mg/kg, p.o.) significantly inhibited both the plasma extravasation and the scratching behavior, suggesting that its inhibitory effects are mediated by the suppression of neuropeptidergic action as well as histaminic action. Olopatadine seems to be a novel-type drug for the treatment of dermatitis.View full abstractDownload PDF (120K)
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