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Volume 84 (1984)
- Issue 6 Pages 471-
- Issue 5 Pages 411-
- Issue 4 Pages 327-
- Issue 3 Pages 259-
- Issue 2 Pages 155-
- Issue 1 Pages 1-
Volume 84, Issue 4
Displaying 1-9 of 9 articles from this issue
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Kazuhiro OHKUBO, Kenichi SUZUKI, Takeshi OTORII1984 Volume 84 Issue 4 Pages 327-335
Published: 1984
Released on J-STAGE: March 07, 2007
JOURNAL FREE ACCESSThe effects of intracerebroventricularly (i.c.v.) administered prostaglandin (PG) E2, F2α, I2 and their precursor, arachidonic acid (AA), on systemic blood pressure were investigated in anaesthetized rabbits. 1) PGE2 (0.03-1 μg/ 0.1 ml/rabbit) elevated blood pressure in a dose-related manner. 2) PGF2α exerted no significant changes on blood pressure. 3) PGI2 (0.3-10 μg/0.1 ml/rabbit) lowered blood pressure in a dose-related manner. 4) AA (0.1-10 μg/0.1 ml/rabbit) dose-independently elevated blood pressure. 5) I.c.v. pretreatment with indomethacin, an inhibitor of cyclooxygenase, abolished the hypertensive effect of AA, but did not influence the hypertensive and hypotensive effect caused by PGE2 and PGI2, respectively. These results suggest that the hypertensive effect of AA may be composed of various actions of the above-mentioned PG and the related substances synthetized from AA in the brain tissues.View full abstractDownload PDF (3851K) -
Shigeo TAMURA, Seiji KUZUNA1984 Volume 84 Issue 4 Pages 337-344
Published: 1984
Released on J-STAGE: March 07, 2007
JOURNAL FREE ACCESSFor the simple assay of anti-inflammatory agents and the analysis of their mode of action, the early inflammatory reactions of the carrageenin abscess model in rats were studied by determining abscess (exudate) weight, vascular permeability measured by extravascular dye leakage, protein, prostaglandins (PGs), and DNA (an index of leucocyte infiltration). Subcutaneous injection of 0.5 ml of 2% carrageenin in the dorsal sacral region of rats induced an edema with an initial weak phase (3 hr) followed by a second pronounced phase, reaching a maximum (2.3 g) at 15 hr and declining steadily thereafter. During the first 15 hr, there was a good correlation between the edema formation and changes in the increased vascular permeability, and also the PGE contents in the exudate paralleled the permeability, but thereafter, these components did not follow the same time course. The marked increase in DNA content in the exudate started after a lag time of a few hr in correspondence with the second accelerated edema formation. The edema formation was effectively inhibited by indomethacin and dexamethasone given simultaneously with the irritant injection; maximum inhibition with indomethacin (2 mg/kg, p.o.) was 36% at 15 hr and 48% with dexamethasone (0.1 mg/kg, p.o.) at 9 hr. Indomethacin very significantly affected exudate PGE levels and vascular permeability, rather than suppressing the edema formation. When the treatment was initiated at 9 hr after injury, it was not effective in reducing the weight of the 24-hr abscess, whereas it had significant effect on the PGE concentration. Dexamethasone did not exert significant effect on the PGE levels despite its potent and steady anti-edematous activities. This carrageenin test may offer a simple method for examining the efficacy and the mode of action of anti-inflammatory agents.View full abstractDownload PDF (4618K) -
Eijiro TAGASHIRA, Keiko MATSUKAWA, Tomoko URANO, Tsutomu SUZUKI, Saizo ...1984 Volume 84 Issue 4 Pages 345-352
Published: 1984
Released on J-STAGE: March 07, 2007
JOURNAL FREE ACCESSThe present study was made to investigate the developmental toxicity of ethanol administered to rat pups via dams for 18 days (day 3-21 after parturition) from the relatively early postnatal stage in terms of changes in the threshold for pentylenetetrazol-induced convulsions, the sleeping time with barbital, preference for morphine or ethanol and tolerance to phenobarbital. The threshold of pentylenetetrazol-induced convulsions in ethanol-experienced offspring were similar to that in the naive group. The sleeping time with barbital in ethanol-experienced offspring were prolonged in comparison with that in the naive offspring. Pups whose dams were treated with ethanol showed high preference for ethanol. The inhibition of rotarod performance in ethanol-experienced offspring were attenuated, namely, the development of tolerance to phenobarbital in ethanol-experienced offspring were accelated. The present results suggest that the inhibition of functional development in the central nervous system may have occurred in the ethanol-experienced offspring.View full abstractDownload PDF (4298K) -
Hiroshi TAKAHASHI, Manabu SHIBATA, Tsuyako OHKUBO, Satoru NARUSE1984 Volume 84 Issue 4 Pages 353-362
Published: 1984
Released on J-STAGE: March 07, 2007
JOURNAL FREE ACCESSFormalin which was said to produce prolonged pain and inflammation was injected subcutaneously into the back of guinea pigs, and minor tremor pain response (MTP-response) was measured using the MT-pick up, integrator and digital volt meter. The MTP-response curve showed a biphasic pattern. Immediately after injection, the MTP-response curve showed a significant peak which lasted for about 2 min (the first phase) and subsequently dipped rapidly, and after 5 min, it began to rise slowly again and had a peak at 30 min (the second phase). Morphine (6 mg/kg, s.c.) inhibited completely the first and second phases. Levallorphan (1.2 mg/kg), however, reversed the inhibitory effect of morphine at the first phase, but not at the second phase. Aspirin (200 mg/kg, i.p.), aminopyrine (100 mg/kg, s.c.) and pentazocine (5 mg-10 mg/kg, s.c.) inhibited significantly the formalin-induced MTPresponse at both phases. Pyridinol carbamate (200 mg/kg, i.p.) and hydrocortisone (25 mg/kg, i.p.) had no effect on the MTP-response at the first phase, but inhibited it at the second phase. There was a parallelism between the time course of the vascular permeability induced by formalin and that of the second phase of MTP-response. From these results, it is suggested that the first phase of MTP-response is derived from the direct effect of formalin on free nerve endings, while the second phase is derived from the inflammation. Since two kinds of pain features were differentiated in this method, the relationships with so-called “immediate pain” and “delayed pain” were discussed. Furthermore, this method can be utilized to assess pain and the action of analgesics objectively and quantitatively.View full abstractDownload PDF (4254K) -
II. Effects on experimental acute pancreatitisMasahiro IWAKI, Masayuki OZEKI, Takuo SATO, Kunihiko SUZUKI, Akemi MOT ...1984 Volume 84 Issue 4 Pages 363-372
Published: 1984
Released on J-STAGE: March 07, 2007
JOURNAL FREE ACCESSEffects of FUT-175, a novel synthetic protease-inhibiting agent, on various models of experimental acute pancreatitis were examined. FUT-175 infused i.v. at a dose range of 5-50 μg/kg/min inhibited the increase in plasma trypsin activity and reduced the mortality of rabbits in trypsin-induced acute pancreatitis in a dose-dependent manner. Increase in serum amylase activity and pancreatic tissue lesion were attenuated in rabbits. In addition, FUT 175 infused i.v. at a dose range of 1-50 μg/kg/min reduced the mortality of rats in experimental acute pancreatitis produced by trypsin and endotoxin. FUT-175 infused i.v. at a dose range of 1-100 μg/kg/min protected the dogs from the increase in plasma trypsin activity and hypotension and shock induced by trypsin, well-known characteristics of acute pancreatitis. These results suggest that FUT-175 is beneficial as a therapeutic agent of acute pancreatitis.View full abstractDownload PDF (5446K) -
III. Anti-inflammatory activities of FUT-175Masahiro IWAKI, Minoru ODA, Masayuki OZEKI, Yoshitaka INO, Kunihiko SU ...1984 Volume 84 Issue 4 Pages 373-384
Published: 1984
Released on J-STAGE: March 07, 2007
JOURNAL FREE ACCESSAnti-inflammatory effects of FUT-175 (nafamstat mesilate), a new synthetic serine protease inhibitor, on various types of experimental inflammation were investigated in vivo and in vitro, in comparison with non-steroidal antiinflammatory drugs (NSAID). The in vivo studies showed that FUT 175 has the abilities to inhibit almost all types of inflammatory reactions employed in the present study. In particular, being evaluated on the basis of the effect of indomethacin, FUT-175 exhibited relatively higher potencies against some reactions such as zymosan-induced increase of vascular permeability, scald paw edema, zymosan-induced granuloma-pouch, the Arthus reaction and acetic acid-induced writhing in which the complement system or the kallikrein-kinin system are considered to play an important role. The in vitro studies showed that FUT-175 is quite different from NSAID, that is, FUT-175 had no effects on heat-induced erythrocyte-lysis and heat-induced denaturation of bovine serum albumin. FUT-175 also had no effect on chemotaxis of polymorphonuclear leucocytes, but inhibited the production of chemotactic factor by antigen-antibody reaction. These above results suggested that FUT-175 has a different mode of action from NSAID and that serine protease inhibiting activities of this compound might play an important role in its anti-inflammatory effect.View full abstractDownload PDF (5997K) -
Combination of HPLC and RIAYoshiyuki IGUCHI, Hiroshi TOKUDA, Shiroh KISHIOKA, Masanobu OZAKI, Sad ...1984 Volume 84 Issue 4 Pages 385-393
Published: 1984
Released on J-STAGE: March 07, 2007
JOURNAL FREE ACCESSA specific and quantitative method for the determination of rat fi-endorphin by the combination of HPLC and RIA was developed. Rabbit antiserum against camel β-endorphin (cβ-E) was raised and used for RIA at the final concentration of 1 : 10000. The quantitative range estimated from the displacement curve was 0.1-2.0 ng. Crossreactivities with Met-Enk, Leu-Enk, α-MSH, α-endorphin, ACTH and human β-E were <0.1, <0.1, <0.1, <0.1, 2 and 100%, respectively. These peptides were separated from each other by revesed phase HPLC with UV254 nm detection, and the minimum detectable dose of c19-E was found to be 1 μg. β-E-like immunoreactivity (β-ELIR) in the HPLC effluent was determined by RIA. The HPLC-RIA chromatogram of authentic cβ-E exhibited a single peak which coincided with the peak of cβ-E detected by UV, and 80% of the injected cβ-E (1-100 ng) was detected in the cβ-E fraction. The HPLC-RIA chromatogram of rat pituitary, hypothalamus, cerebrospinal fluid and plasma revealed the presence of 1-3 peaks, one of which was observed at the position of cβ-E. The HPLC elution of rat pituitary resolved the material into two peaks of biological activity, one of which coincided with the peak of β-ELIR at the position of cβ-E. The HPLC-RIA chromatogram of the cβ-E fraction from pituitary obtained by gel-chromatography exhibited three peaks, one of which coincided with cβ-E. These results suggest that β-ELIR in the cβ-E fraction of the HPLC elution may reflect rat β-E accurately.View full abstractDownload PDF (4303K) -
Miwa MISAWA, Tomokazu HOSOKAWA, Junzo KAMEI, Saizo YANAURA, Yuichi FUJ ...1984 Volume 84 Issue 4 Pages 395-406
Published: 1984
Released on J-STAGE: March 07, 2007
JOURNAL FREE ACCESSThe effects of oxybutynin, an anticholinergic and antispasmodic agent, on the cardiovascular system were studied in comparison with those of atropine in anesthetized dogs. Oxybutynin (0.1-10 mg/kg, i.v.) caused a transient hypotension, tachycardia, increases in femoral, stomach, mesenteric and common carotid arterial blood flows and a decrease in renal arterial blood flow. Atropine (0.1-10 mg/kg, i.v.) caused a stronger and more prolonged hypotension with bradycardia, accompained by weaker blood flow changes than those by oxybutynin. In open-chest dogs, oxybutynin caused increases in cardiac output and coronary sinus outflow and decreases in heart rate and left ventricular pressure. The agent augmented dLVP/dt/P at doses up to 3 mg/kg, i.v., but reduced it at 10 mg/kg, i.v. Atropine caused stronger cardiosuppressive responses than those of oxybutynin. Coronary sinus outflow was decreased by atropine, unlike in the case of oxybutynin. The pressor responses of norepinephrine, epinephrine and tyramine were potentiated by pretreatment with oxybutynin (15 mg/kg, i.v.). However, pressor or depressor responses induced by histamine, isoproterenol, serotonin and DMPP were unaffected by oxybutynin. Intraarterial injections of oxybutynin, atropine and papaverine caused femoral and renal arterial vasodilations dose-dependently, in the following order of potency: papaverine>oxybutynin>atropine. In the isolated blood-perfused canine papillary muscle preparation, oxybutynin and atropine caused a negative inotropic action, whereas papaverine caused a positive inotropic action. From the above results, it is suggested that oxybutynin has milder cardiosuppressive and hypotensive effects than atropine in terms of potency and duration of action, and in addition, oxybutynin has a vasodilating action probably ascribable to its anticholinergic and antispasmodic actions.View full abstractDownload PDF (5950K) -
Masahiro SUNO, Masaki SHIBOTA, Akinobu NAGAOKA1984 Volume 84 Issue 4 Pages 407-410
Published: 1984
Released on J-STAGE: March 07, 2007
JOURNAL FREE ACCESSThe effects of CV-2619 on the half-life and hemolysis of red blood cells (RBC) in stroke-prone spontaneously hypertensive rats (SHRSP) were examined. The half-life of RBC in SHRSP was shorter than that in control Wistar Kyoto rats (WKY) and was significantly prolonged in SHRSP kept on a diet containing 0.1 % (w/w) of CV-2619 (calculated at 71.0 mg/kg/day): 11.7±0.4 days in untreated SHRSP (n=11) ; 13.8±0.1 days in treated SHRSP (n=5, P<0.01); and 14.8±0.5 days in WKY (n=6). The hemolysis of RBC in salt-loaded SHRSP was accelerated compared with that in WKY. In SHRSP given CV-2619 (20 or 70 mg/kg/day, p.o.) for 2 weeks, the hemolysis was significantly inhibited; the percent hemolysis was 43.9±0.9% (n=10) in the control, 39.5±0.9% (n=9, P<0.01) in the group given 20 mg/kg CV-2619, and 37.1±0.8% (n=9, P<0.001) in the group given 70 mg/kg CV-2619. These results suggest that the stabilizing effect of CV-2619 on the membrane of RBC is involved in its therapeutic effects in cerebral vascular disorders.View full abstractDownload PDF (2199K)
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