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Sachiko NAKANO, Munekazu GEMBA
1989 Volume 50 Issue 2 Pages
87-92
Published: 1989
Released on J-STAGE: August 25, 2006
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Effects of
cis-diamminedichloroplatinum II (cisplatin), an antitumor agent with a dose-limiting effect of nephrotoxicity, on lipid peroxides and glutathione (GSH) were examined in rat kidney cortical slices treated with or without diethylmaleate (DEM), a GSH depletor, in vitro. DEM (3 mM) decreased the GSH level to about 16% of the control with a concomitant increase in lipid peroxides after 90 min of incubation. The same effects were obtained with 1 mM cisplatin 90 min later. Cisplatin (1 mM) with DEM (2 mM) stimulated both the decrease in GSH and the increase in lipid peroxides 90 min after incubation. However, cisplatin with DEM markedly stimulated lipid peroxidation with a small effect on the GSH decrease by cisplatin alone 30 min after incubation, while each drug by itself did not affect lipid peroxidation. The antioxidants
N, N'-diphenyl-
p-phenylenediamine (DPPD), promethazine, and ascorbic acid abolished cisplatin-induced lipid peroxidation in the presence of DEM. DPPD had no effect on the depletion of GSH caused by cisplatin and DEM. Ascorbic acid and promethazine caused only a slight return towards the control level. The results suggested that cisplatin-induced lipid peroxidation is due to another mechanism in addition to the GSH depletion caused by the antitumor drug.
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Hiroshi TSUCHIHASHI, Takafumi NAGATOMO, Shoichi IMAI
1989 Volume 50 Issue 2 Pages
93-100
Published: 1989
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The preference by bunitrolol for β
1 and β
2-adrenoceptors of the rat brain, heart and/or lung was assessed by the radioligand binding assay method with
125I-iodocyanopindolol (
125I-ICYP) or
3H-CGP12177. Scatchard plots of
125I-ICYP binding in the presence of bunitrolol were found to be non-linear. The inhibition constants (K
j) of bunitrolol for high (β
2-) and low affinity sites (β
1-) were: 0.42±0.16 nM for β
1 and 3.55±1.61 nM for β
2 (β
1 > β
2), respectively. Displacement experiments conducted with the preparations of the rat brain using
125I-ICYP or with the preparations of the rat heart using
3H-CGP12177 yielded K
j values for bunitrolol of 0.53±0.20 (β
1) and 2.37±0.78 (β
2) nM for
125I-ICYP binding and 2.01±0.38 (β
1) and 12.67±6.54 (β
2) nM for
3H-CGP12177 binding. In addition, the K
j value for 5HT
1B-receptors assessed in displacement experiments conducted with
125I-ICYP in the presence of 30 μMI-metoprolol in the rat brain was 10.54±5.92 nM. Thus, bunitrolol is a β
1-selective antagonist.
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Yukio HIRAYAMA, Sonoko TSUCHIDA, Ritsuko KURATA, Yumiko KATSUTA, Kaoru ...
1989 Volume 50 Issue 2 Pages
101-110
Published: 1989
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The oral administration of 2-(1, 3-dithiol-2-ylidene)-1-phenyl-1, 3-butanedione (KZ-1026) to normal rats at doses of 50, 100 and 200 mg/kg/day for 3 days accelerated liver enlargement in association with a dose-dependent increase in the total amounts of protein, RNA and DNA in the liver. The liver weight at 24 hr after the third dose of 200 mg/kg reached 174% of the control. With respect to the effect on liver enlargement, KZ-1026 differed from phenobarbital, since KZ-1026, unlike phenobarbital, increased hepatic DNA content without significant effects on P-450 and aminopyrine-N-demethylase. Incorporation of [
3H]thymidine into liver DNA was stimulated by a single dose of KZ-1026 (200 mg/kg), and it peaked at 24 hr post dose (18 times the control), followed by an increase in the number of liver nuclei. Liver growth was also accompanied by an increasing hepatic reserve cell mass, expressed by the capacity of eliminating exogenous galactose from the blood stream. Pretreatment with KZ-1026 (200 mg/kg/day) for 3 days significantly improved the survival rate of subtotally hepatectomized rats from 39% to 78%. These findings indicate that KZ-1 026 accelerates hepatocyte proliferation, resulting in an enhancement of liver functional mass in normal rats.
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Kiyoshi KURIYAMA, Yoshiyuki HIYAMA, Kiyoshi ITO
1989 Volume 50 Issue 2 Pages
111-118
Published: 1989
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Antiallergic effects of 4-[2-oxo-3-(1 H-tetrazol-5-yl)-2H-chromen-8-yloxy]-butyric acid (C4C) were studied. C4C is an active principal metabolite of an orally effective antiallergic agent, KP-136. C4C (0.2-1 mg/kg, i.v.) markedly inhibited the mast cell-mediated homologous PCA of rats and the experimental allergic asthma of rats and guinea pigs, although it had almost no effects on heterologous PCA and compound 48/80-induced cutaneous response in rats. C4C (0.2 mg/kg, i.v.) was scarcely effective on cutaneous responses induced by intradermal injection of histamine and serotonin which are principal chemical mediators of rat homologous PCA, and it blocked the decrease of skin histamine content after the PCA. In addition, C4C (0.01-0.5 μg/ml) inhibited the increase of
45Ca uptake of mast cells, the histamine release and the degranulation induced by the antigen-antibody interaction. These effects of C4C were much the same as those of KP-136. From the above findings, C4C is considered to be an antiallergic agent that inhibits the mast cell activation by blocking the calcium influx, and it shares similar pharmacological properties with KP-136.
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Yoshie MATSUI, Satoshi KASHII, Masashi SASA, Shuji TAKAORI, Yoshihito ...
1989 Volume 50 Issue 2 Pages
119-124
Published: 1989
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Effects of ethanol on optokinetic, vestibular and caloric nystagmus were investigated in pigmented rabbits to determine whether or not it affects a specific site involved in the induction of various nystagmus. Optokinetic nystagmus was produced by rotation of the drum with vertical stripes at an angular velocity of 0.85°/sec. Vestibular nystagmus was induced by horizontal rotation at an angular velocity of 30°/sec and caloric nystagmus by infusion of cold water into the external meatus. Cumulative injection of ethanol into the auricular vein to doses of 0.1, 0.2, 0.4 and 0.8 g/kg inhibited both vestibular and caloric nystagmus dosedependently, but did not affect the optokinetic nystagmus. These results suggest that relatively low doses of ethanol mainly act on the peripheral vestibular organ and impair the vestibular function without affecting the optokinetic system.
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Hiroyuki FUKUI, Atsushi HAYASHI, Hiroshi FUKUDA, Motohiko TAKEMURA, At ...
1989 Volume 50 Issue 2 Pages
125-130
Published: 1989
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Dependency of histamine induced phasic and tonic contractions on intracellular and extracellular calcium in guinea pig tracheal smooth muscle was investigated. In Ca
++-free Krebs-Ringer solution, the phasic contraction caused by 10
-5 M histamine was not affected, but the tonic contraction declined much faster than that in normal Krebs-Ringer solution (KR). The phasic contraction in KR containing 3×10
-4 M dantrolene was depressed, but reached a level similar to that in normal KR, and the tonic contraction was maintained similarly with or without dantrolene. In KR containing organic calcium channel blockers, 10
-5M nilvadipine (FR34235), 10
-5 M verapamil or 10
-5 M diltiazem, neither phasic contraction nor tonic contraction was affected. No contraction was observed in Ca
++-free KR containing 3×10
-4 M dantrolene. These results suggested that the phasic con traction by histamine depended on the intracellular calcium and the tonic one, on the extracellular calcium, and the organic calcium channel blockers had no effect on both phasic and tonic contractions caused by histamine.
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Tsuneichi HASHIMOTO, Misa KIMORI, Yoshiko NAKAMURA, Kinya KURIYAMA
1989 Volume 50 Issue 2 Pages
131-139
Published: 1989
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Effects of oral administration of NC-1100 on the metabolism of neuroactive amino acids in rat brain were studied using stroke-prone spontaneously hypertensive (SHR-SP) and Wistar Kyoto rats. The repeated administration of NC-1100 induced a significant increase of γ-aminobutyric acid (GABA) content in the cerebellum and medulla oblongata of SHR-SP. The decrease of aspartic acid contents in the cerebellum and medulla oblongata of SHR-SP was also noted following NC-1100 administration. Although the activity of L-glutamic acid decarboxylase did not change in these cerebral areas, the activity of GABA-transaminase:succinic semialdehyde dehydrogenase was found to be significantly reduced in the cerebellum of SHR-SP following the repeated administration of NC-1100. The turnover rate of GABA was also significantly reduced in the cerebellum and medulla oblongata of SHR-SP. It was also found that the spontaneous release of preloaded [
3H]GABA from cerebral cortical slices was significantly retarded by the continuous oral administration of NC-1100. These results suggest that NC-1100 may be a drug inducing the increase of GABA in the cerebellum and medulla oblongata following continuous administration, especially in animals having hypertension associated cerebrovascular disorders such as SHR-SP.
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Masahiko OGIHARA
1989 Volume 50 Issue 2 Pages
141-147
Published: 1989
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Effects of calcium channel blockers from structurally different classes and hydralazine on epinephrine-induced hyperglycemia were studied in vivo. Nifedipine (0.05-0.20 mg/kg, i.p.) and nicardipine (0.40-0.80 mg/kg, i.p.) markedly potentiated the epinephrine-induced hyperglycemia in a dose-dependent manner. In contrast to these dihydropyridine calcium channel blockers, verapamil and diltiazem did not significantly affect the epinephrine-induced hyperglycemia at doses of 0.10-1.0 mg/kg, i.p. At higher doses (10 mg/kg, i.p.), significant potentiation of epinephrine-induced hyperglycemia was observed by these non-dihydropyridine calcium channel blockers. Hydralazine also markedly increased the epinephrine-induced hyperglycemia. These calcium channel blockers and hydralazine had no significant effect on the basal plasma glucose levels at any dose used here. As judged from the rates of glucose disappearance (K values), dihydropyridines significantly impaired the glucose tolerance in much lower doses than those of non-dihydropyridines and hydralazine. Furthermore, epinephrine-induced impairment of glucose tolerance was markedly potentiated by these calcium channel blockers and hydralazine at doses which potentiated the epinephrine-induced hyperglycemia. These results suggest that, at least in part, the potentiation of epinephrine-induced hyperglycemia by dihydropyridines, non-dihydropyridines and hydralazine is related to the inhibition of peripheral glucose utilization produced by insulin.
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Yosuke TOJYO, Yoshito MATSUMOTO, Kazuhiko OKUMURA, Masaaki KANAZAWA
1989 Volume 50 Issue 2 Pages
149-157
Published: 1989
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Using dispersed rat parotid cells, the effects of three calmodulin antagonists, trifluoperazine (TFP), N-(6-aminohexyl)-5-chloro-1-naphthalenesulfonamide (W-7), and N-(6-aminohexyl)-1-naphthalenesulfonamide (W-5), on amylase release and acinar cell structure were examined. TFP and W-7 strongly inhibited both isoproterenol (ISO) and dibutyryl cyclic AMP-stimulated amylase release at a concentration of 50 or 100μM, while W-5, a weak calmodulin antagonist, had only little effect. Cyclic AMP level was markedly elevated by ISO even in the presence of TFP or W-7. These results indicate that the calmodulin antagonists affect amylase release at steps distal to cyclic AMP metabolism. Electron micrographs demonstrated that treatment of parotid cells with either TFP or W-7 caused a loss of luminal microvilli and surface folds. When cells were stimulated by ISO in the presence of TFP or W-7, the enlarged lumina did not recover to their original size and the discharged secretory material was retained in the lumina. Numerous secretory granules remained in the acinar cytoplasm. W-5 affected the acinar cell structure only a little. These observations lead to the assumption that TFP and W-7 interfered with the normal functions of the cytoskeletal system. It is proposed that calmodulin may he involved in the exocytosis of parotid amylase through the regulation of the cytoskeletal system.
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Keiko KAWAMOTO, Kiyohisa UCHIDA
1989 Volume 50 Issue 2 Pages
159-165
Published: 1989
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NADH-dependent vitamin K reductase activity in rat liver microsomes was measured by detecting the amount of the reduced form of vitamin K from the oxidized form of the vitamin. The enzyme activity was not detected when intact microsomes were employed as the enzyme source, but the solubilization of the microsomal enzyme with 1.5% Triton X-100 caused a development of the activity. Although the enzyme activity decreased gradually with time after the solubilization, the enzyme was stabilized by the addition of 20% glycerol and 2 mM vitamin C. Some optimal assay conditions for the vitamin K reductase were determined using the solubilized enzyme, and the standard assay method is described. Vitamin K reductase activity was not affected by warfarin and N-ethylmaleimide (NEM), but pyridoxal-5-phosphate (PAL-P) inhibited the activity, especially when microsomes were preincubated with PAL-P. The enzyme activity was not inhibited by N-methyltetrazolethiol (NMTT) and NMTT-containing antibiotics, suggesting that the hypoprothrombinemia caused by β-lactam antibiotics was not due to the inhibition of NADH-dependent vitamin K reductase.
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Mariko NISHIYAMA, Tetsuro KUGA
1989 Volume 50 Issue 2 Pages
167-173
Published: 1989
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Effects of a potent neurotropic mycotoxin, fumitremorgin A (FTA), on the spinal cord were studied, using rabbits lightly anesthetized with urethane and chloralose. Spontaneous discharges of L
7 spinal ventral roots and common peroneal nerves were increased after intravenous injection of 100-200 μg/kg of FTA. Their abnormal discharge pattern represented the convulsive effect of FTA. Spinal monosynaptic reflexes became irregular in amplitude, with a slight predominance of smaller reflexes. Polysynaptic reflexes were inhibited in many cases. These FTA-induced changes in ventral root discharges and spinal reflexes were abolished by spinal transection at a segment of the upper level. These results suggest that FTA may have no direct facilitatory action on spinal motoneurons and that its remarkable motor effect has its origin in the supraspinal central nervous system.
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Takayasu ASAMI, Hisashi KURIBARA
1989 Volume 50 Issue 2 Pages
175-184
Published: 1989
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Behavioral effects of 6R-L-erythro-5, 6, 7, 8-tetra hydrobiopterin (R-THBP), a co-factor for tyrosine hydroxylase and tryptophan hydroxylase, were investigated by means of ambulatory activity in mice. Single administration of R-THBP (50 and 100 mg/kg, s.c.) showed no significant effect on the mouse's ambulatory activity for 5 hr. The ambulation-increasing effect of methamphetamine (2 mg/kg, s.c.) was dramatically enhanced and prolonged by the pretreatment with R-THBP (100 mg/kg, s.c.) 0, 2, 6, 12 and 24 hr before, but not 18 or 36 hr before, the methamphetamine administration. However, when combined administration of R-THBP (100 mg/kg, s.c., 2 hr before) with methamphetamine (2 mg/kg, s.c.) was repeated at intervals of 3-4 days, the enhancement by R-THBP of the methamphetamine effect was observed only in the 1st and 2nd administration, but not in the later administration. The pretreatment with R-THBP (100 mg/kg, s.c., 2 hr before) enhanced the ambulation-increasing effect of ephedrine (80 mg/kg, i.p.), but failed to modify those of cocaine (20 mg/kg, s.c.), mazindol (2.5 mg/kg, s.c.), bromocriptine (8 mg/kg, i.p.), morphine (20 mg/kg, s.c.) and scopolamine (0.5 mg/kg, s.c.). It is noteworthy that R-THBP differentially modifies the ambulation-increasing effect of the above-mentioned drugs.
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Takaki KOGA, Yasuyuki SHIRAKI, Kazushige SAKAI
1989 Volume 50 Issue 2 Pages
185-193
Published: 1989
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The pharmacological properties of SGB-1534, 3-[2-[4-[(
o-methoxy phenyl)-1-piperazinyl]ethyl]-2, 4(1H, 3H)]-quinazolinedione monohydrochloride, a selective α
1-adrenoceptor antagonist, compared with prazosin, phentolamine and yohimbine, were examined in contractile responses of isolated canine mesenteric arteries and veins and femoral arteries and veins to exogenous noradrenaline. The arteries and veins concentration-dependently contracted when exposed to noradrenaline. The sensitivity to noradrenaline, when compared in terms of pD
2 values, was significantly higher in the veins than in the arteries. Phentolamine and yohimbine were competitive antagonists against noradrenaline in the arteries and the veins. SGB-1 534 and prazosin caused a parallel shift to the right of the con centration-response curves for noradrenaline only in the arteries: the two antagonists were less effective in the veins than in the arteries when low concentrations of noradrenaline were applied. The pharmacological characteristics of SGB-1534 resemble those of prazosin. The pA
2 values for SGB-1534 against noradrenaline in the arteries were much higher than those for prazosin, phentolamine and yohimbine. The result indicates that SGB-1 534 may predominantly act upon arterial resistance vessels rather than the venous side, resulting in potent hypotension.
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Yozo HORI, Hisao HATAKEYAMA, Katsutoshi YAMADA, Atsushi KUROSAWA
1989 Volume 50 Issue 2 Pages
195-205
Published: 1989
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The effects of S-145, a newly synthesized thromboxane A
2 (TXA
2) receptor antagonist, were studied on collagen-induced changes of electrocardiograms (ECG) in rats and thrombocytopenia in rats and mice. Intravenous injection of collagen induced abnormal ECG changes such as elevation or depression of the ST segment, arrhythmia and in severe cases, cardiac arrest. These changes peaked at 3-5 min and lasted for 10 min. S-145 showed remarkable improvement of the ECG changes by both intravenous and oral administration, and the action lasted over 4 hr with 10 mg/kg, p.o. Reference compounds ONO-3708, dazoxiben and aspirin also improved the ECG changes significantly, but ticlopidine was ineffective. S-145 prevented the collagen-induced thrombocytopenia in rats but did not affect the increase in plasma TXB
2 levels. S-145 also prevented collagen-induced thrombocytopenia in mice after either intravenous or oral administration in a dose dependent manner. The efficacy of S-145 was 4-13 times greater than those of the reference compounds, and the duration of action was over 4 hr with 10 mg/kg, p.o. These results indicate that S-145 is a potent, orally active and long-lasting TXA
2 receptor antagonist, which will be promising as a drug for thromboembolism and ischemic heart disease caused by platelet activation.
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Shigekatsu W. KOHNO, Hiroshi HASHII, Keiko OGINO, Hideki YAMAMURA, Kat ...
1989 Volume 50 Issue 2 Pages
207-216
Published: 1989
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The effect of oxitropium bromide (Ba253), a quaternary scopolamine derivative, on the resting tonus and agonist-induced contraction of isolated guinea pig airway smooth muscle and on the anaphylactic release of histamine and immunoreactive leukotrienes (i-LTs) from lung fragments were investigated and compared with those of Sch1000, atropine and isoproterenol. Ba253 dosedependently inhibited the acetylcholine (ACh)-induced contraction of the isolated trachea and lung parenchyma. The degree of inhibitory potency was similar to that of Sch1000 and 10 times higher than that of atropine. Ba253 minimally influenced the resting tonus or contractions induced by other agonists including histamine, serotonin and LTD
4. Sch1000 and atropine had similar or slightly stronger inhibitory effects on the tonus and contractions than Ba253. On the other hand, low concentrations of isoproterenol solely relaxed the resting tonus and inhibited the the agonist-induced contractions of both preparations. Neither Ba253 nor Sch1000 inhibited the anaphylactic release of histamine and LTs from both guinea pig and human lung fragments, but both mediator releases from either species were slightly inhibited with dose-dependency by atropine and potently inhibited by isoproterenol. From these results, it is suggested that Ba253 is a relatively specific antagonist to cholinergic receptors and might be possibly effective as an inhalant for asthma.
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Den'etsu SUTOO, Kayo AKIYAMA, Naoyuki FUJII, Kazuhiro MATSUSHITA
1989 Volume 50 Issue 2 Pages
217-227
Published: 1989
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The effects of various divalent cations on the Ca
2+-binding sites of calmodulin were observed by 400 MHz
1H-NMR. The first and second Ca ions bound to sites III and IV (stage I), while the third and fourth bound to sites I and II (stage II). Zn
2+, Hg
2+ and Mn
2+ bound to the first and third Ca
2+-binding sites, but not to the second and fourth. Zn
2+, Hg
2+ or Mn
2+ coula bind to the first Ca
2+-binding site by themselves and could bind to the third site only after the conformational change which occurs when two Ca
2+ ions bind to first and second sites. Although Mg
2+ did not bind to the first, second or fourth Ca
2+-binding sites, it did bind to the third site. These results suggest that the order of Ca
2+-binding and the order of affinity of the binding sites are not parallel; the first and third Ca
2+-binding sites have high Ca
2+-affinity, with the third being highest, whereas the second and fourth sites are of lower affinity. Also, we suggest in this study that the first and second sites are exposed on the surface of the protein, while the third and fourth ones are buried in the interior; the latter are exposed by the conformational change accompanying the binding of calcium to the first and second sites. Furthermore, the form of the interface by which calmodulin binds to target enzyme was altered slowly and continuously by the calcium-induced conformational change. The target enzyme was chosen and bound selectively to calmodulin among various enzymes by each interface form.
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Kanji IZUMI, Ryoichi NAGATA, Toshiro MOTOYA, Jun-ichi YAMASHITA, Tamin ...
1989 Volume 50 Issue 2 Pages
229-233
Published: 1989
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The continuous infusion of taurine markedly protected against paraquat (PQ)-induced oliguria in beagles. Pharmacokinetic studies revealed that taurine infusion increased the blood concentration of PQ and reduced the net content in the kidney and, to a lesser extent, in the lung. The excretion of PQ into the urine was unaltered. The infusion of glycine did not have such effects.
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Makoto KATORI, Toshiji KANAYAMA, Kouji SASAKI, Akinori UENO, Miwako TA ...
1989 Volume 50 Issue 2 Pages
234-238
Published: 1989
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An initial increase (3-12 hr) in the polymorphonuclear leukocytes (PMN) counts after ligation of the rat left main coronary artery was reduced by 49.4% (at 12 hr) by a 5-lipoxygenase inhibitor, AA-861 (80 mg/kg, p.o., 1 hr before ligation). Depletion of the complement components induced by cobra venoma factor (CVF) (i.v.), given one day before, resulted in significant reduction in the PMN accumulation after 12 hr (by 63.6% at 24 hr). The combined treatment (CVF+AA-861) suppressed the PMN accumulation by 69.7% (24 hr). The infarct size at 48 hr was also reduced by approximately 36% by either AA-861, CVF or combined treatments.
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Haruko SUGINO, Hideyo SHIMADA
1989 Volume 50 Issue 2 Pages
239-242
Published: 1989
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The effects of diltiazem on plasma uric acid level (P
UA) and renal uric acid excretion were investigated in oxonate-loaded rats. Diltiazem (0.5 mg/kg, i.v.) decreased P
UA without producing uricosuria, and it decreased fractional excretion of uric acid and renal blood flow. The present results suggest that diltiazem produces hypouricemia not accompanied by uricosuria, probably by affecting uric acid metabolism, and it may also cause an alteration in the renal handling of uric acid partly due to changes in renal hemodynamics.
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Leonora Rivera PANCHO, Ikuko KIMURA, Ryoichi UNNO, Masayasu KURONO, Ma ...
1989 Volume 50 Issue 2 Pages
243-246
Published: 1989
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The effects of crude and processed ginger extracts and pungent components, S-(+)-[6]-gingerol and [6]-shogaol, on noradrenaline (NA) and prostaglandin (PG) F
2α-induced contraction were investigated using mouse mesenteric veins. Both spicy constituents inhibited the contractile responses to NA. Crude ginger extract and S-(+)-[6]-gingerol potentiated the PGF
2α-induced contraction, whereas processed ginger extract and [6]-shogaol inhibited the contraction.
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Nobuyuki FUKUISHI, Munekazu GEMBA
1989 Volume 50 Issue 2 Pages
247-249
Published: 1989
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The nephrotoxicity of cisplatin was evaluated in an in vitro system with an established cell line of normal rat kidney, NRK-52E. Leakage of enzymes from the cells into the culture medium increased when they were exposed to 1 μM of cisplatin for 72 hr. The level of lipid peroxides increased in the cells after 48 hr of exposure to cisplatin; the increase was more rapid than the enzyme leakage. This culture system can be used to evaluate drug-induced nephrotoxicity and its mechanism.
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Akira SAITO, Takuya NAKAZAWA
1989 Volume 50 Issue 2 Pages
250-252
Published: 1989
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Subarachnoid hemorrhage (SAH) was simulated in dogs by injecting blood into the cisterna magna. Time-dependent development of spasm of the basilar artery was angiographically determined. One week after SAH, the diameter of the basilar artery decreased by 15.5±5.4% and 46.4±3.0% in the single and double injection model, respectively. Thereafter, the artery diameter gradually returned to normal. The time course of diameter changes in the double injection model resembles that seen in the clinical setting, and the double injection model seems to be useful for the experimental study of cerebral vasospasm.
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