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Volume 100, Issue 1
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Kenji ONODERA1992 Volume 100 Issue 1 Pages 1-9
Published: 1992
Released on J-STAGE: February 13, 2007
JOURNAL FREE ACCESSWhen rats were maintained on a thiamine-deficient diet for 30 days, about 70% of the animals showed a mouse-killing response (muricide). The thiamine-deficient killer-rats do not eat but merely killed the mice. Once this abnormal behavior appeared, the response remained, and could not be suppressed by the administration of thiamine hydrochloride plus thiamine-supplemented diet, regardless of a return to normal feeding, growth and heart rate. Drugs that activate the central serotonergic and noradrenergic systems have suppressive effects on it. Conversely, among the various depletions of brain monoamines, only depletion of serotonin by the drug p-chlorophenylalanine significantly increased the incidence of muricide. Antihistaminergic drugs were potently effective, but atropine, an anticholinergic drug, were ineffective. Various antidepressants and electroconvulsive shock treatment also suppressed muricide to various degrees. Thus, it is expected that the muricide induced by thiamine deficiency may be useful as an animal model of depression, although the usefulness of this abnormal behavior as a working model of depression or for screening new antidepressants remains to be evaluated.View full abstractDownload PDF (20132K) -
Yoshiaki YAMASHITA, Yoshimasa MIYAKE, Shigeo MITSUHIRO, Tatsuo FURUKAW ...1992 Volume 100 Issue 1 Pages 11-20
Published: 1992
Released on J-STAGE: February 13, 2007
JOURNAL FREE ACCESSThe effects of ifenprodil on adenosine triphosphatase (ATPase) activity were examined using guinea pig liver mitochondria. 1) Intact mitochondrial ATPase activity was stimulated by ifenprodil in a concentration-dependent manner, this effect being further potentiated with dinitrophenol. The stimulation by ifenprodil appeared with only ATP among four nucleotides as substrate. Mg2+ and Ca2+ attenuated the effect of ifenprodil. Ifenprodil abolished the KCN-induced inhibition. 2) Heat-treated mitochondrial ATPase activity, kept for 60 min at 50°C, was decreased in a concentration-dependent manner by ifenprodil. The inhibitory effect of ifenprodil was abolished by Mg2+ and Ca2+. These results indicate that ifenprodil has two behaviors, acceleration of a latent ATPase and inhibition of an activated ATPase. These findings, together with our previous data, suggest that ifenprodil seems to affect the actions of Mg2+ and Ca2+ on mitochondrial ATPase by directly affecting the membrane, and these mechanisms may be involved in its anti-cyanide effect.View full abstractDownload PDF (21483K) -
Masaya TAKAHASHI, B. FRITZ-ZIEROTH, Motonori YAMAGUCHI, Hiroshi OGAWA, ...1992 Volume 100 Issue 1 Pages 21-28
Published: 1992
Released on J-STAGE: February 13, 2007
JOURNAL FREE ACCESSCerebral lesions accompanying stroke in male stroke-prone spontaneously hypertensive rats (SHRSP, n=10) were examined by both magnetic resonance imaging (MRI) and histological evaluation. T2-weighted MR images (T2-WI), taken 1-2 days after animals showed behavioral hyperactivity, indicated hyperintense regions in the occipital cortex, caudate putamen and/or thalamus. The areas of hyperintensity on T2-WI corresponded to neurodegenerative regions including edema, gliosis, and softening of the tissue. T1-weighted images (T1-WI) did not show any hyperintense regions. Howerer T1-weighted images enhanced by the contrast media Gd-DTPA (Gd-T1-WI) showed hyperintense spots within some of the hyperintense areas on T2-WI, which exhibited neurodegenerative regions such as thrombus, angionecrosis and hemorrhage in addition to the edematous formation. The hyperintense areas on Gd-T1-WI were smaller than those on T2-WI. In some animals, hypointense spots on T2-, T1-and Gd-T1-WI were found within the hyperintense areas, which corresponded to clots. Extensive histological examination did not reveal any additional cerebral degeneration which had not been detected on the MR images. These findings indicate that MRI is useful for detecting and differentiating various types of cerebrovascular disease in this model.View full abstractDownload PDF (20361K) -
Makoto MAYANAGI, Sadao NAKAYAMA, Katsuji OGUCHI1992 Volume 100 Issue 1 Pages 29-37
Published: 1992
Released on J-STAGE: February 13, 2007
JOURNAL FREE ACCESSThe effects of hot water extracts (HWEs) from 15 kinds of Compositae herbs and distanninized fractions (DTFs) from 9 of theses herbs on rat hepatic lipid peroxidation (LPO) and the activities of aminopyrine N-demethylase (APD) and aniline hydroxylase (ANH) were examined in vitro. The APD activity was inhibited by HWEs from 12 herbs, of which the effect of HWE from Inchinko was remarkable. Inhibitory effects of DTFs from Inchinko, Gaiyo, Kantoka, Sojutsu and Byakujutsu on the APD activity were smaller, if any, than those of the corresponding HWEs, whereas DTF from Koka enhanced the activity of APD. The ANH activity was inhibited by HWEs from 11 herbs. HWEs from Inchinko, Gaiyo and Senpukuka increased the ANH activity, whereas the DTFs from them caused inhibition. The inhibitory effect of DTF from Shion on the ANH activity was smaller than that of the corresponding HWE, but the effects of DTFs from Koka, Byakujutsu, Sojutsu and Mokko were larger than those of the respective HWEs. LPO was inhibited by HWEs from 14 herbs, of which the HWEs from Inchinko, Gaiyo, Kantoka, Koka and Mokko caused marked inhibitions. Except in the case of Shion, the inhibitory effects of DTFs on LPO were smaller than those of the corresponding HWEs, whereas DTF from Koka still showed a marked inhibition. In the present experiments, it is suggested that Inchinko, Gaiyo, Koka, Kikuka, Senpukuka, Byakujutsu, Sojutsu and Mokko, which showed remarkable effects on LPO and the activities of APD and ANH, might also exert their effects in vivo.View full abstractDownload PDF (16896K) -
Takeshi SUGAYA, Satoshi MINOBE, Tomoyasu TANIGUCHI, Yoshikatsu HASHIMO ...1992 Volume 100 Issue 1 Pages 39-45
Published: 1992
Released on J-STAGE: February 13, 2007
JOURNAL FREE ACCESSImidapril is a newly synthesized non-sulfhydryl-containing angiotensin I converting enzyme (ACE) inhibitor. The present study describes the inhibitory effects of imidapril and its active metabolite 6366A on ACEs from various tissues and compares its effects to those of captopril, enalapril and enalaprilat in vitro. 6366A inhibited swine renal and human serum ACEs with an inhibition constant (Ki) of 0.067 nM and 0.04 nM, respectively. These values were 3 to 18 times more potent than those of the other inhibitors. The kinetic study showed that 6366A exerted competitive type inhibition. The ACE inhibition (IC50 values) of 6366A, enalaprilat and the structurally related compounds (6366DM and 6366PY) were compared in homogenates of lung, aorta, heart, brain and kidney from spontaneously hypertensive rats (SHRs) and Wistar Kyoto rats (WKYs). The inhibitory effects of 6366A on all tissue ACEs from SHRs and WKYs were the most potent among these compounds. And the inhibitory potencies of these compounds were correlated with their chemical structure. The present results suggest that 6366A may show a strong inhibitory effect on ACEs from several tissues and species due to its chemical characteristics.View full abstractDownload PDF (14223K) -
Mutsuyoshi KAZAMA, Kunio KOBAYASHI, Chieko TAHARA, Yukari MIYAJIMA, Yu ...1992 Volume 100 Issue 1 Pages 47-58
Published: 1992
Released on J-STAGE: February 13, 2007
JOURNAL FREE ACCESSDisseminated intravascular coagulation (DIC) is a severe syndrome associated with generalized, intractable bleeding and multiple organ failure. Synthesized protease inhibitors such as gabexate mesilate and nafamostat mesilate show an improving effect on DIC, which develops by a chain reaction involving the coagulation, fibrinolysis, complement and kallikrein systems. Experimental DIC was developed in Beagle dogs by infusion of 150 U/kg tissue thromboplastin (Group I), and the improving effect of a new synthetic protease inhinbitor, E-3123, was examined. The following groups of animals were treated with drugs: Group II (n=4) was given with 5 mg/kg/hr of E-3123; group III (n=4) was given 10 mg/kg/hr of E-3123; and group IV was given 6 mg/kg/hr of gabexate mesilate (GM). Although improvement of the hemodynamics or peripheral circulation was not apparent, a slight, but insignificant, improvement of lactate/pyruvate was noted in the treated groups. On the other hand, the hemostatic abnormalities such as prolongation of prothrombin time and activated thromboplastin time; decreases of platelet count, fibrinogen and α2-antiplasmin; and increases of fibrin degradation products were significantly improved in the treated groups. These results indicate that E-3123 is effective for improving experimental DIC, and it is suggested that E-3123 is applicable for the treatment of clinical DIC.View full abstractDownload PDF (24285K) -
Masayuki NIWA, Masakatsu NOZAKI, Masashi KOBAYASHI, Kaito TSURUMI1992 Volume 100 Issue 1 Pages 59-66
Published: 1992
Released on J-STAGE: February 13, 2007
JOURNAL FREE ACCESSThe affinity of a 1, 4-dihydropyridine (DHP) type calcium channel blocker, NZ-105 ((±)-2-[benzyl(phenyl)amino]ethyl 1, 4-dihydro-2, 6-dimethyl-5 (5, 5-dimethyl-2-oxo-1, 3, 2-dioxaphosphorinan-2-yl)-4-(3-nitrophenyl)-3-pyridinecarboxylate hydrochloride ethanol), on the DHP-binding site in the central nervous system and various receptor sites were compared with nicardipine and diltiazem by the use of a receptor binding assay technique. NZ-105 exhibited a displacement effect against [3H]nimodipine in the rat brain DHP-binding site with a potency similar to that of nicardipine. Nicardipine also inhibited the specific binding of several other [3H]-labelled ligands to their receptor such as adrenergic α1, α2, β, dopamine D1, D2, opioid μ, δ, and κ-type receptors. Diltiazem also showed a similar inhibitory property. However, NZ-105 showed only weak inhibition against the binding to these receptors. These results suggest that Z-105 has strong affinity to the DHP-binding site in voltage-dependent calcium channels with higher specificity.View full abstractDownload PDF (16640K) -
Yasuhiko KITOH, Tsuneo KATSURAMAKI, Hirokazu TANAKA, Michiko TANAKA, N ...1992 Volume 100 Issue 1 Pages 67-76
Published: 1992
Released on J-STAGE: February 13, 2007
JOURNAL FREE ACCESSSodium hyaluronate (HA) with a molecular weight of approximately 600, 000 ?? 1, 200, 000 is, reportedly effective against osteoarthritis (OA). However, since HA with higher molecular weight is expected to be more effective against OA, we investigated the effects of HA (SL-1010) newly produced by fermentation with a molecular weight of 1, 800, 000 ?? 2, 100, 000 on the experimental OA induced by intraarticular injection of papain, into the knee joint of the rabbit, in comparison with those of HA with a molecular weight of about 950, 000 (HA-95). When 0.4, 0.8, and 1.6% papain (0.5ml) was injected into the knee joint of the animal twice with a 3-day interval, there were dose-dependent degenerative changes and a decrease in sulfated glycosaminoglycan (S-GAG) in the articular cartilage with slight synovial inflammatory changes 6 weeks after the final injection of papain. In this OA model, intraarticular application of SL-1010 slightly reduced the degeneration of articular cartilage, compared with the injections of HA-95 or saline (control). SL-1010 also caused a significant recovery in the S-GAG level which was decreased in the cartilage of the OA model, compared with the control. In addition, SL-1010 inhibited the release of 35S-GAG from the cartilage obtained from normal and OA model joints. These results suggest that SL-1010 is effective in inhibiting the degeneration of cartilage in the OA model, probably due to the recovery of the S-GAG level by reducing the release of S-GAG from the cartilage.View full abstractDownload PDF (25740K) -
Hirokazu TANAKA, Yasuhiko KITOH, Tsuneo KATSURAMAKI, Michiko TANAKA, N ...1992 Volume 100 Issue 1 Pages 77-86
Published: 1992
Released on J-STAGE: February 13, 2007
JOURNAL FREE ACCESSEffects of SL-1010 on the experimental osteoarthritis (OA) produced by intra-articular injection of papain, proteolytic enzyme, in the knee joint of the guinea pigs were histologically and biochemically investigated. In addition, experimental conditions to produce OA in guinea pig knee joint were also examined, since papain-induced OA has been mainly studied in rabbits. Six weeks after intra-articular injection of papain (1 %, 0.1 ml), there were inflammatory reactions of the synovial membrane, degenerative changes in chondrocytes and the matrix of the articular cartilage, a decrease in the Safranin-O staining intensity and lowering of sulfated glycosaminoglycan. Electronmicroscopic observations revealed that the amorphous layer had disappeared and large bundles of unit collagen fibers and larger collagen fibers had appeared in the cartilage matrix. In the OA model, SL-1010 reduced the inflammatory reactions of the synovial membrane, inhibited development of degenerative changes in chondrocytes and the matrix of the articular cartilage and recovered the Safranin-O staining intensity. The sulfated glycosaminoglycan contents in the cartilage was significantly increased in the SL-1010-treated group, compared with the control group. The electronmicroscopically observed charges in the papain-injected knee joint of the control group were rarely detected in the SL-1010-treated group. These results suggest that SL-1010 inhibits degenerative changes in the chondrocytes and the matrix probably by reducing synovial inflammation and protection of the cartilage in the OA model of guinea pigs.View full abstractDownload PDF (34324K) -
Itaru OHOI, Naomi OZAWA, Keita NAKAMURA1992 Volume 100 Issue 1 Pages 87-95
Published: 1992
Released on J-STAGE: February 13, 2007
JOURNAL FREE ACCESSThe influence of ischemic zone size and hemodynamics on the reperfusion-induced arrhythmia in the anesthetized rat heart was examined. The heart was subjected to regional ischemia for 4 min by the occlusion of LAD followed by reperfusion for 7 min. After the reperfusion, 64% of the rats died due to irreversible VF. The size of the ischemic zone, the increase in heart rate during ischemia and the incidence of ischemic arrhythmia (VPBs and/or VT) of the animals that died after the reperfusion were significantly greater or higher than those of the surviving animals. There were positive correlations between the size of the ischemic zone and the increase of heart rate during ischemia and the incidence of ischemic arrhythmia. These results indicate that the size of the ischemic zone is a main factor that determines the degree of reperfusion-induced arrhythmia and also contributes to the increase in heart rate and the occurrence of arrhythmia during ischemia. Therefore, in addition to monitoring the blood pressure, heart rate and electrocardiogram, measurement of the size of the ischemic zone is essential for the evaluation of drug effects on reperfusion-induced arrhythmia using this animal model.View full abstractDownload PDF (20837K)
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