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Volume 73, Issue 5
Displaying 1-12 of 12 articles from this issue
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Hideo MIZUSAWA, Tsuyoshi NAGASE, Hiroshi FUJIWARA, Ken SAKAI, Eiichi S ...1977 Volume 73 Issue 5 Pages 517-526
Published: 1977
Released on J-STAGE: March 29, 2007
JOURNAL FREE ACCESSEffects of ifenprodil (2-(4-benzyl-piperidino)-1-(4-hydroxyphenyl)-l-propanol) on the circulatory and central nervous system were examined in male Sprague-Dawley strain rats treated with ifenprodil 50 and 200 mg/kg/day p.o. for 5 to 30 days. Dose of 200 mg/kg/day slightly inhibited body weight gain for 30 days. Both doses of the drug decreased motor activity and produced a myorelaxation of extremities, ptosis and salivation in a dose-dependent manner; the animals gradually became tolerant to the drug when such was administered repeatedly. Ifenprodil 50 and 200 mg/kg/day consistently lowered systolic blood pressure in conscious rats during the prolonged daily treatment, but reflex tachycardia associated with hypotension tended to decline during the treatment. Neither vasopressor response to noradrenaline nor vasodepressor response to ifenprodil in anesthetized rats after 30 days administration differed as compared with data in control animals. In the aorta isolated from rats treated for 30 days with ifenprodil, the contractile response to noradrenaline was approximately the same as seen with controls, and pA2 values of ifenprodil against noradrenaline in control and experimental aortas did not differ. Ifenprodil produced hypothermia, and this effect was attenuated during daily treatment with ifenprodil. Ifenprodil decreased contents of noradrenaline in the cerebral cortex, brain stem, heart and aorta, and of dopamine in whole brain during continuous oral treatment for 1 to 30 days, however, serotonin content in whole brain remained unchanged. Ifenprodil 10-6 ?? 10-4 M inhibited the uptake of noradrenaline in isolated hypothalamus by 20 ?? 96%, while desmethylimipramine 10-6 M and phentolamine 10-4 M inhibited this uptake 76 and 59%, respectively. It may be concluded that hypotensive, a-adrenergic receptor blocking and noradrenaline-depleting actions of ifenproil are not altered during prolonged oral treatment with ifenprodil.View full abstractDownload PDF (4385K) -
Anti-inflammatory activity of benzo[c] phenanthridine derivatives and possible mechanisms of action.Heitaroh IWATA, Itaru YAMAMOTO, Tohru MASUKAWA, Keiji KOMORIYA, Hideo ...1977 Volume 73 Issue 5 Pages 527-539
Published: 1977
Released on J-STAGE: March 29, 2007
JOURNAL FREE ACCESSOf five newly synthesized benzo(c)phenanthridine derivatives tested, the two compounds, BPD-I and BPD-II were found to have potent anti-edematous activity with intraperitoneal administration to S.D. rats. BPD-I showed a marked inhibitory effect against acute inflammation such as induced rat paw edema and leucocyte emigration and protein exudation by means of CMC pouch method and capillary permeability enhancement induced by various phlogists. This compound also inhibited subacute and chronic inflammatory responses such as granuloma formation induced by croton oil or cotton pellet. The anti-inflammatory activities of this compound resembled those of hydrocortisone. The inhibitory effects of carragenan edema and capillary permeability enhancement by ATP were strikingly reduced in adrenalectomized rats suggesting involvement of the hypophysis-adrenal systems. Rat serum corticosterone level and hepatic tyrosine aminotransferase activity (TAT) were then measured after BPD-I injection. The serum corticosterone level was increased and shortly after the elevation of corticosterone, hepatic TAT levels also increased. Thus it is concluded that the corticosterone release from adrenal gland plays a role in the anti-inflammatory action of BPD-I.View full abstractDownload PDF (5486K) -
Masayuki ARAKAWA, Tamotsu KONDO, Hiroki MITSUI, Shigeo SUZUKI, Motohar ...1977 Volume 73 Issue 5 Pages 541-547
Published: 1977
Released on J-STAGE: March 29, 2007
JOURNAL FREE ACCESSThe mechanisms of glycerol-induced hemolysis and inhibition of the lysis by fructose were studied. Energy of activation, entropy of activation, and free energy of activation for the hemolytic process were calculated from the data on temperature change in the rate of hemolysis. The values of the thermodynamic quantities thus obtained indicated that the temperature change in the rate of hemolysis is brought about mainly by that in the viscosity of liquid. The presence of fructose in the hemolytic systems caused a reduction in both energy of activation and entropy of activation while free energy of activation remained almost unchanged. Pretreatment of erythrocytes with glycerol gave rise to complete hemolysis of the cells in hypotonic as well as hypertonic saline solutions. Thus, it appears that glycerol releases a portion of the lipids of the cell membrane into the surrounding medium and dehydrates the membrane, thereby promoting hemolysis. Fructose was considered to prevent dehydration of the membrane by glycerol.View full abstractDownload PDF (2550K) -
Motohiko UEDA, Saburo MATSUDA, Hiroshi TAKEDA1977 Volume 73 Issue 5 Pages 549-556
Published: 1977
Released on J-STAGE: March 29, 2007
JOURNAL FREE ACCESSIn anesthetized Beagle dogs, intravenous bolus administration of dobutamine (DOB) caused an increase of systolic pressure and a decrease of diastolic pressure — increase of pulse pressure. These effects of DOB were not so pronounced as the marked depressor effect of isoproterenol (Iso) and pressor effects of epinephrine (Epi), norepinephrine(NE) and dopamine (DA). The degree of the positive chronotropic effect of DOB was the same as that of DA. Incidences of ventricular extrasystole observed at the maximal dosages of catecholamines, intravenous administration of 300 μg/kg of DOB, 3 of Iso, 10 of Epi, 10 of NE, and 300 of DA, were 1/4, 1/4, 4/4, 4/4, and 2/4, respectively. With no evidence of ventricular extrasystoles, an increase of pulse pressure was also observed in conscious dogs given an intravenous infusion of DOB (10 or 30 μg/kg/min for 20 min). Iso infusion resulted in an increase of serum free fatty acid, and a decrease of serum Na and K. Although DA infusion increased blood glucose and serum free fatty acid, DOB infusion produced no significant concentration change of blood components. These experimental results indicate that effects of DOB on the blood pressure, heart rate, and several blood components are weaker than other catecholamines.View full abstractDownload PDF (3475K) -
Yukio HARA, Setsuo TOMIZAWA1977 Volume 73 Issue 5 Pages 557-569
Published: 1977
Released on J-STAGE: March 29, 2007
JOURNAL FREE ACCESSThe paper disk granuloma (PDG) method is a newly devised procedure for the screening of antiinflammatory drugs and was compared with the cotton pellet (CP) method. Results obtained were as follows; in the CP method, formation of granuloma was observed on the 1st day after the implantation of CP. On the 3rd day, maximum weight, protein and nucleic acids in granuloma were observed. The granuloma produced by PDG method was too small to collect on the 1st day. Weight and protein content of granuloma reached the peak on the 2nd or 3rd day. With respect to nucleic acids, maximum amounts were found on the 6th day. The incorporation of 3H-uridine into RNA was increased in the early stage of the formation of granuloma in both methods. The maximum incorporation of 3H-thymidine into DNA was noted on the 2nd day in CP method, and on the 3rd day in PDG method. Development of granuloma in the PDG method was different from that in CP method with respect to the synthesis of DNA. Antigranuloma action of fluocinolone acetonide (FA) was more marked in the PDG method than in the CP method, suggesting that the PDG method is more sensitive for, screening of antiinflammatory drugs. Granuloma produced by the PDG method was also prevented and therapeutically suppressed by certain non-steroidal antiinflammatory drugs. ED50 values of applied FA, phenylbutazone, and 3-o-phthaloxy glycyrrhetinate were 27 μg/kg, 91 mg/kg, and 66 mg/kg, respectively.View full abstractDownload PDF (6722K) -
Ken-ichi SASAKI, Masaaki SAITOH, Hiroaki KAWAUCHI, Giichi TAKAYANAGI1977 Volume 73 Issue 5 Pages 571-578
Published: 1977
Released on J-STAGE: March 29, 2007
JOURNAL FREE ACCESSEffects of egg lectins from Rana japonica (RJ-lectin) and from Rana catesbiana (RC-lectin) on the growth of Ehrlich solid tumor were investigated in male ddY mice. The antitumor activity was estimated by weighing the solid tumor on the 10th day after the cell inoculation (1 × 106 cells). Intraperitoneal or subcutaneous administration of RJ-lectin (10 ?? 40 mg/kg) suppressed the tumor growth, and the inhibitory action of RJlectin was dose dependent. RJ-lectin at 10, 20, or 40 mg/kg (three intraperitoneal administrations) suppressed the tumor growth, the inhibition rate being 35, 56, or 69%, respectively, RC-lectin at a dose of 2.5, or 5.0 mg/kg (single intraperitoneal administration) also suppressed the growth, to a certain extent. The phagocytic activity in the mice was not changed by successive administration of RJ-lectin. Leakage of dye into the peritoneal cavity of mice increased with intraperitoneal injection of RJ-lectin after the intravenous injection of pontamine sky blue. This leakage also increased with RJ-lectin (1 mg) even in the immunosuppressive mouse treated with hydrocortisone. RJ-lectin is the first animal origin lectin to reveal an antitumor activity. RJ-lectin may therefore have a direct cytotoxic effect on tumor cells.View full abstractDownload PDF (4395K) -
Yukio HARA, Setsuo TOMIZAWA1977 Volume 73 Issue 5 Pages 579-590
Published: 1977
Released on J-STAGE: March 29, 2007
JOURNAL FREE ACCESSAntigranuloma effect of fluocinolone acetonide (FA) administered subcutaneously was studied using the paper disk granuloma method in rats. Results obtained were as follows: Antigranuloma effect of FA was not affected by adrenalectomy. The wet weight and protein contents of granuloma were diminished by FA. The incorporation of leucine into the protein of the granuloma was maximum on the 3rd day, decreased rapidly on the 4th day, and was markedly inhibited by FA. Contents of RNA and DNA in the granuloma were diminished after FA administration, and the ratio of RNA/DNA was reduced. FA notably inhibited the in vitro incorporation of orotate into RNA. Addition of FA in vitro inhibited the incorporation of uridine into RNA, especially into microsomal RNA, but had no influence on the incorporations of leucine into protein and thymidine into DNA of granuloma. A single administration of FA inhibited the incorporation of uridine, leucine and thymidine. Puromycin administered into the granuloma inhibited the in vitro incorporation of leucine. Pre-treatment with puromycin influenced the inhibitory effect of FA on the in vitro incorporation of thymidine, while post-treatment with puromycin had no influence on this effect of FA. Our findings suggest that the antigranuloma effect of FA is due to inhibition of RNA synthesis, and that the inhibitory effect of FA on synthesis of DNA may be mediated by specific protein(s) induced by FA.View full abstractDownload PDF (6023K) -
Yoichiro HAMADA, Iwao SATO, Keizo ITO, Shinichi KUWABARA, Yasuo KOJIMA ...1977 Volume 73 Issue 5 Pages 591-596
Published: 1977
Released on J-STAGE: March 29, 2007
JOURNAL FREE ACCESSEffects of acebutolol on carbohydrate and lipid metabolism in rats and on adenylate cyclase of heart and liver in dogs were investigated to determine the β receptor blocking properties of the compound. Acebutolol exhibited the β blocking activity and inhibited the increase of serum lactate concentration induced by adrenaline. This inhibition was about one-sixth as potent as that of propranolol. In hyperglycemic and free fatty acid effects of adrenaline, acebutolol inhibited the adrenaline-induced free fatty acid increase more effectively than hyperglycemia induced by adrenaline. In the inhibition of stimulated adenylate cyclase activity in the heart and liver, acebutolol was more active on the heart than on liver. Relative β1 specificity of acebutolol was 93.2. Inhibition of propranolol on adenylate cyclase activity was more potent than that of acebutolol on both tissues, but showed no specificity. These results suggest that acebutolol is β1 selective, although its β blocking potency is less than that of propranolol.View full abstractDownload PDF (2530K) -
Yuichi SAITOH, Kazuo ICHIHARA, Yasushi ABIKO1977 Volume 73 Issue 5 Pages 597-603
Published: 1977
Released on J-STAGE: March 29, 2007
JOURNAL FREE ACCESSEffects of coronary artery ligation on myocardial glycogenolysis were studied in the endo and epicardial layers of the left ventricular wall in dogs pretreated with 10 or 100 μg/kg (i.v.) of carteolol, a potent beta-adrenergic blocking agent. Coronary artery ligation was performed by ligating one of the small branches of the left anterior descending coronary artery. In control (saline-pretreated) dogs, an increase in phosphorylase a activity and an increase in breakdown of glycogen were observed in both endo and epicardial layers after coronary artery ligation. In the presence of 10 or 100 μg/kg of carteolol, however, increases in phosphorylase a activity and increase in breakdown of glycogen were not observed in either the endo or epicardial layers. These results indicate that pretreatment of the dog with carteolol inhibits the increase in glycogenolysis caused by coronary artery ligation. Nevertheless, carteolol did not completely inhibit the coronary artery ligationinduced increase in glucose-6-phosphate and lactate levels, and the coronary artery ligation-induced decrease in phosphocreatine level, particularly in the endocardial layers.View full abstractDownload PDF (3139K) -
Yoshitoshi KASÉ, Takashi YAKUSHIJI, Hakaru SEO, Moriyuki SAKATA ...1977 Volume 73 Issue 5 Pages 605-624
Published: 1977
Released on J-STAGE: March 29, 2007
JOURNAL FREE ACCESSPerry and Boyd's method described in 1941 appears to be the most suitable for evaluating the efficacy of expectorants. In this method, changes in volume of respiratory tract fluid (RTF) collected by postural drainage from animals breathing air kept at a constant temperature and humidity are used as criteria. We attempted to improve on the method and to establish the optimum experimental conditions for rabbits. Accordingly, an air conditioning apparatus and tracheal cannula were re-designed and basic experimental conditions essential for quantitative collection of RTF were studied. Using this method, the effects of drugs on the volume of respiratory tract fluid (VRTF) were determined. Bromhexine and emetine as expectorants increased VRTF, and the former showed far more remarkable effects. Codeine and dextromethorphan as antitussives, isoproterenol, clorprenaline and C-78 as bronchodilators decreased VTRF. On the other hand, fominoben and eprazinone as antitussives increased VRTF. Our findings with application of this new approach indicate that this method is applicable for evaluating not only the efficacy of expectorants which increase VRTF but also that of other drugs which decrease VRTF.View full abstractDownload PDF (9780K) -
Keisetsu SHIMA, Toshiji MIYAGAWA, Shinobu SAKURADA, Kensuke KISARA1977 Volume 73 Issue 5 Pages 625-631
Published: 1977
Released on J-STAGE: March 29, 2007
JOURNAL FREE ACCESSEffects of morphine (1mg/kg i.v.) were examined on evoked potential of somatosensory afferent pathways elicited by tooth pulp stimulation in cats. Results were as follows: In central gray (CG) of the midbrain which has a triphasic evoked potential with a short latency, morphine decreased the amplitude. In nucl. lateralis posterior(LP) and nucl. medialis dorsalis(MD) of the thalamus, association relay nuclei, which have a late component followed by a fast component with a relatively short latency, morphine decreased the amplitude of the late component but not that of fast component of the evoked potential. In nucl. centralis lateralis(CL) of the thalamus, intralaminar nuclei, and pre-central association area(PCA) of the cortex, which have monophasic and triphasic evoked potentials with a long latency, respectively, morphine markedly decreased the amplitude of both evoked potentials. In nucl. ventralis posteromedialis(VPM) and somatic sensory area I (SI), lemniscal system, which has biphasic and mutiphasic evoked potentials with a short latency, respectively, morphine had no effect on the these evoked potentials. As these depressant effects of morphine on evoked potentials were antagonized by naloxone (0.2mg/kg i.v.), a specific morphine action is suggested.View full abstractDownload PDF (3269K) -
Kaito TSURUMI, Masakatsu NOZAKI, Kazumasa NAKANO, Koichiro GO, Hajime ...1977 Volume 73 Issue 5 Pages 633-650
Published: 1977
Released on J-STAGE: March 29, 2007
JOURNAL FREE ACCESSIt has been already reported that ketoprofen (KP) has a potent anti-inflammatory action comparable to indomethacin, but with oral administration, gastric mucous membrane disturbances occur. In the present work, we administered the Na salt of KP (KP-Na) subcutaneously and found that the anti-inflammatory action was more potent in subacute and chronic inflammations than in the acute one. As an acidic compound, KP-Na had a relatively potent analgesic-antipyretic action and a medical efficacy comparable to the usual non-steroidal anti-inflammatory drugs given orally. The efficacy in case of subcutaneous administration was 2 to 3 times stronger over both acute and chronic inflammations than in case of oral administration. On the other hand, the gastric mucous membrane disturbance was decreased to about 1/3 in case of subcutaneous administration, thus the gastric disturbance could be abated and the medical efficacy can be increased when KP-Na is given subcutaneously. As KP-Na was less irritative at the injection site, the compound could be used clinically for a subcutaneous administration.View full abstractDownload PDF (7836K)
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