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Volume 76, Issue 7
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Kazuko NONAKA, Akira UENO1980 Volume 76 Issue 7 Pages 549-552
Published: 1980
Released on J-STAGE: March 29, 2007
JOURNAL FREE ACCESSCardiovascular studies on conscious laboratory animals are required for an accurate assessment in drug evaluations. However, attempts to define pharmacological significance of an agent in conscious and unrestrained animals have been limited by the techniques available for recording the cardiovacsular parameters. We designed a system which can be applied to record biological pressure, such as the blocd pressure, using a miniature FM-FM radio-transmitter and a receiver demodulator. The transmitter consists of a differential amplifier capable of an input signal up to 3×106 times, voltage controlled oscillator which triggers a 2-5 volts range and 76-90 MHz transmitting oscillator. The transmitter requires a 5.6 V mercury battery. Earphone output of a commercial FM radio-receiver serves for signals to the demodulator. The demodulator is based on the phase locked loop principle and is equipped with an independent output for instantaneous wave recording and the mean of this recording. Transmitting distance of the system may depend on the receiver, however, in most instances, the distance is over 30 meters, in an open field. Accuracy of the telemetering data is dependent on discharge characteristics of the mercury battery. After discharging 5%, the full capacity of the cell gives a sufficient zero stability and accurate pressure measurements.View full abstractDownload PDF (4329K) -
(I) Morphological changes during the early stage of thiamine deficiencyEmiko OGUCHI, Masako OKAZAKI, Reiko HOBARA, Masahiko HAJIKANO, Hitoshi ...1980 Volume 76 Issue 7 Pages 553-565
Published: 1980
Released on J-STAGE: March 29, 2007
JOURNAL FREE ACCESSWe observed under light and electron microscopes morphological changes in the rat sciatic nerve during the early stages of a thiamine deficient state as induced by a pyrithiamine (PT: 50 μg/100g × 6 days) and thiamine deficient diet (TDD). We simultaneously determined thiamine levels in the whole sciatic nerve of rats. Experiments were undertaken with normal control, TDD (rats fed a TDD), PT (PT treated rats) and PTD (PT treated rats fed a TDD) groups. Microscopically, there were numerous shrunken myelinated axons with myelin ovoids or folds in the PT group and many swollen ones in the PTD group. Electron microscopically, we found more advanced lesions in the PTD group than in the other groups. These ultrastructural changes were swelling of Schwann cells, enlarged rough-surfaced endoplasmic reticulum, axonal degeneration with shrinkage, loss of organelle or abnormal myelin sheath, and proliferation of fibroblasts. The thiamine level in the PTD group decreased to 18 ?? 30% that of control in proportion to the morphological changes. On the other hand, the thiamine level in the PT group (55 ?? 61%) decreased slightly more than that of the TDD group (50 ?? 56%), but changes in morphology were vice versa. These results suggest that the morphological changes in the sciatic nerve caused by PT-induced thiamine deficiency differs from changes seen in cases of dying-back neuropathy caused by TDD-induced deficiency, and that PT itself directly affects the nervous system.View full abstractDownload PDF (27856K) -
(II) Morphological changes during the last stages of thiamine deficiencyEmiko OGUCHI, Masako OKAZAKI, Minoru NOUMI, Koji SAKAMOTO1980 Volume 76 Issue 7 Pages 567-580
Published: 1980
Released on J-STAGE: March 29, 2007
JOURNAL FREE ACCESSWe observed under light and electron microscopes morphological changes in the rat sciatic nerve during the last stages of a thiamine deficient state as induced by pyrithiamine (PT: 50 μg/100g × 11 days) and thiamine deficient diet (TDD), in which rats experienced severe tetanic convulsions. Experiments were undertaken with normal control, PT (PT treated rats) and PTD (PT treated rats fed a TDD) groups. Grossly, 4 out of 9 rats in the PTD group had severe tetanic convulsions on the 12th day and there were no neurolcgic signs in the PT group. Microscopically, many of the myelinated axons in the animals in the PT group showed shrinkage with myelin ovoids and folds, but in the PTD group, there was swelling as well as shrinkage. Despite the difference in general-symptoms between the PT and PTD groups, axonal degeneration in the both groups, as determined electron microscopically was almost to the same degree and the convulsed rats in the PTD group showed the severest changes in the myelin sheath. These ultrastructural changes included swelling or vacuolation of Schwann cells, axonal degeneration with the appearance of a myelin like structure, collecticn of neurctubules or vacuoles, invasion of Schwann cell or/and myelin fragments into the periaxcnal space, and active phagocytosis by the macrophages. These results suggest that PT directly affects the nervous system and that the dysfunction of the sciatic nerve following PT-induced thiamine deficiency originates from the central nervous system.View full abstractDownload PDF (26686K) -
Hiroshi SATOH, Naohisa FUKUDA, Hisashi KURIKI, Yoshitaka MAKI, Masahar ...1980 Volume 76 Issue 7 Pages 581-594
Published: 1980
Released on J-STAGE: March 29, 2007
JOURNAL FREE ACCESSStable ERG was successfully recorded using a contact lens-type electrode in conscious cynomolgus monkeys restrained in a monkey-chair with a specially devised head-holder. After adaptation to darkness, single photostimulation evoked ERG consisting of an initial negative wave (a-wave), followed by a positive wave superimposed with oscillatory potentials (b-wave), and a late positive wave (c-wave). The former two waves were clearly recorded but c-wave was often mixed with artifacts probably due to eye movements. Amplitudes and peak latencies of a- and b-waves increased in progression of dark adaptation and attained to maximum within 20 min. The optimal intensity of photostimulus and time-constant for recording stable a- and b-waves with intermediate amplitudes were found to be 2 joule and 0.1 sec, respectively. The amplitudes and peak latencies (mean ± s.d.) of a- and b-waves obtained by these conditions were 163.3 ± 44.9 and 437.0 ± 37.9μV, and 17.3 ± 0.5 and 53.5 ± 3.2 msec, respectively. These waves were reproducible within 25% variations in amplitude when measured repeatedly for 6 weeks. Anesthetics affected b-wave of ERG without significant change in a-wave: pentobarbital increased the amplitude of b-wave, whereas ketamine reduced this amplitude. A 3-day treatment with 1, 5-di(p-aminophenoxy)pentane (200 mg/kg/day, p.o.), a retinal toxic compound, resulted in complete loss of ERG and visually evoked potential, accompanied with mydriasis and behavioral signs of visual dysfunction. Histological abnormality of the retina was also detected. These results indicate that this technique is useful for recording ERG in order to evaluate the effect of chronically treated drugs on visual perception in conscious monkeys.View full abstractDownload PDF (18022K) -
Anti-inflammatory activity of a topical glucocorticoid, fludroxycortide tape in experimental animalsHideo NAKAMURA, Satoru MOTOYOSHI, Katsumi ISHII, Yasuhiro SETO, Masana ...1980 Volume 76 Issue 7 Pages 595-607
Published: 1980
Released on J-STAGE: March 29, 2007
JOURNAL FREE ACCESSFludroxycortide tape is a thin plastic tape which contains a synthetic glucocorticoid, fludroxycortide of 4 μg/cm2. Fludroxycortide tape with a topical application of 1 cm2 inhibited significantly contact hypersensitivities to oxazolone and picryl chloride in the ear skin of mice and PCA caused by IgE-like antibodies in the depilated abdominal skin of rats. Topical application of 1 to 4 cm2 of fludroxycortide tape produced a significant inhibition against histamine-induced vascular permeability, skin edema induced by intradermal injection of carrageenin into the depilated back and ear edema induced by topical application of croton oil in rats. Topical application of 0.1 to 10 μg/ear of fludroxycortide resulted in a marked decrease of contact hypersensitivity to oxazolone in dose-dependent manner, and had no thymolytic action, while in a dose of 100 μg/ear, thymus atrophy occurred. Ear edema induced by croton oil was markedly inhibited by topical application of fludroxycortide (0.4 μg/ear). Thus, fludroxycortide tape has topical anti-inflammatory activity against both allergic and non-allergic inflammation in mice and rats, and the topical anti-inflammatory activity of fludroxycortide appears to be favourably dissociated from its thymolytic action.View full abstractDownload PDF (19178K) -
Haruo OHNISHI, Chihiro ITO, Kazuo YAMAGUCHI, Kazuo SUZUKI, Akira SAITO ...1980 Volume 76 Issue 7 Pages 609-619
Published: 1980
Released on J-STAGE: March 29, 2007
JOURNAL FREE ACCESSThe potency of anti-inflammatory and ulcerogenic activities of a new anti-inflammatory agent, (10-methyl-7-methoxy-2-phenothiazinyl)-2-propionic acid (protizinic acid, PRT), was compared with those of various known non-steroidal anti-inflammatory agents in 5 experimental models. The ED30 of PRT in carrageenin edema with oral administration was 18.0 mg/kg and its potency was third following indomethacin (IM) and diclofenac sodium (DF), among the 15 agents tested. The ED50 of PRT in ultraviolet erythema with oral administration and the IC50 in protein denaturation were 1.07 mg/kg and 0.89×10-5M, respectively and the activities were the most potent among all agents. The IC50 of PRT in platelet aggregation induced by arachidonic acid was 5.55×10-5M and the rank of potency was sixth following to IM, DF, flufenamic acid, aluminium flufenamate and mefenamic acid (MF). Furthermore, the ED50 of PRT in ulcerogenic activity was 52.3 mg/kg and ranked fifth following azapropazone, MF, alclofenac, metiazinic acid (MA), except for basic agents, mepirizole, benzydamine hydrochloride and tiaramide hydrochloride. Thus, PRT seemed to have a relatively weak ulcerogenic activity in contrast to potent anti-inflammatory activity. Also, PRT was superior to MA, an analogue of PRT, in potency of anti-inflammatory activity, in all experimental models.View full abstractDownload PDF (11975K) -
Morio KANNO, Haruaki NAKAYA, Yuichi HATTORI, Takashi IZUMI, Taiichi NI ...1980 Volume 76 Issue 7 Pages 621-632
Published: 1980
Released on J-STAGE: March 29, 2007
JOURNAL FREE ACCESSCardioselective property of the β-adrenoceptor blocking action of atenolol and its effect on the AV conduction, the atrial muscle refractory period and the cardiac contractility were studied in comparison with these of propranolol. A ratio of pA2 values obtained in the isolated right-atrial preparations and the isolated tracheal preparations of guinea pigs demonstrated that atenolol was highly cardioselective, while propranolol was nonselective. This cardioselective property of atenolol was confirmed in in vivo experiments using guinea pigs. Atenolol increased the AV conduction time and decreased the cardiac contractility dose-dependently in anesthetized dogs of which the heart was electrically driven at fixed rates. At 140 beats/min, AV block was observed at 10 mg/kg, i.v. in 3 of 8 dogs, and further increase in a dose to 30 mg/kg resulted in acute heart failure in one of remaining 5 dogs, while propranolol, though showing a tendency to be less potent in depressing AV conduction in a dose range less than 0.3 mg/kg, produced a state of heart failure in 2 of 5 dogs at 3 mg/kg, i.v. and AV block in all of the remainder at 10 mg/kg, i.v. Functional refractory period of AV node as well as functional and effective refractory period of the atrial muscle were increased dose-dependently by atenolol and propranolol. There were no significant differences between both drugs regarding these effects. Further increase in a pacing rate to 160 and 180 beats/min augmented the depressing effect of both drugs on the AV conduction.View full abstractDownload PDF (16649K) -
Hisashi IDA1980 Volume 76 Issue 7 Pages 633-654
Published: 1980
Released on J-STAGE: March 29, 2007
JOURNAL FREE ACCESSGeneral pharmacological properties of BD 40A, a new bronchodilator agent, were investigated and the following results were obtained. BD 40A showed no effect on the central nervous system, and little effect on the autonomic nervous system. BD 40A produced an increase in heart and respiration rates, a decrease in blood pressure, and change in ECG in both anesthetized dogs and conscious animals. These effects of BD 40A were inhibited by propranolol (β-blocker) administration. BD 40A potentiated carbohydrate and lipid metabolism in Beagle dogs. The pharmacological profile of BD 40A was similar to that of hexoprenaline which was used as the reference compound.View full abstractDownload PDF (25755K) -
Nobuaki HORI, Nobuo KATSUDA, Hiroyoshi NISHI1980 Volume 76 Issue 7 Pages 655-665
Published: 1980
Released on J-STAGE: March 29, 2007
JOURNAL FREE ACCESSThe protective effect of suloctidil [MY 103, erythro-1-(4-isopropylthiophenyl)-2-n-octylaminopropanol] against cerebral hypoxia was investigated in terms of survival time under normobaric hypoxia (96% N2+4% O2 gas mixture) in mice and evoked potential in prepyriform cortex of guinea pig in vitro. In a hypoxic condition, the pretreatment with MY 103 (3.0-12.5 mg/kg, i.p.) resulted in a marked and dose-dependent prolongation of survival time of mice without any adverse effect. The prolongation of survival time was statistically significant at doses over 6.3 mg/kg. The amplitude of evoked potential to electrical stimulation of olfactory tract in the brain slice was consistently and reversibly suppressed by the perfusion with low oxygen Ringer's solution containing about 45% O2 of normal Ringer's solution. This amplitude reduction after 6 minutes exposure to hypoxic perfusate, was consistently reproducible in the same preparation. Preincubation of brain slices in normal Ringer's solution containing 10-7-10-6 g/ml MY 103 for 15 min, however, effectively prevented the hypoxic reduction of the amplitude of evoked potentials to 30-50% of the control experiments. The above data indicate that MY 103 exerts its anti-anoxic effect presumably through modified metabolic processes such as active oxygen or glucose uptake by the brain.View full abstractDownload PDF (12329K) -
Hiromi IIZUKA, Shoichi IMAI1980 Volume 76 Issue 7 Pages 667-674
Published: 1980
Released on J-STAGE: March 29, 2007
JOURNAL FREE ACCESSEffects of guanfacine, a new centrally acting antihypertensive drug, on the central nervous system were studied in mice and rats, and findings compared with those of clonidine. In mice, guanfacine caused slight hypersensitivity and marked piloerection at 4 or 16 mg/kg, p.o. Clonidine exhibited the same symptoms as guanfacine, but at a higher dose elicited severe central excitation such as clonic convulsion. Such central depressive effects as hyposensitivity and catalepsy were, however, observed following administration of both drugs, at the same dose levels, to rats. Clonidine showed a tendency to prolong hexobarbital sleeping time in mice, but such was not observed with guanfacine. Both drugs markedly suppressed responses to nociceptive stimuli in mice. The spontaneous cortex and hippocampus electroencephalograms were respectively changed to high amplitude-slow waves and desynchronized waves by administration of either guanfacine or clonidine at 2 mg/kg, i.v. in curarized rats. Spontaneous motor activity was reduced by both drugs. Both drugs, especially clonidine, caused a fall in body temperature. Both drugs failed to inhibit convulsions induced by electric shock and by intraperitoneally administered pentylenetetrazol. From these results it was concluded that the central effects of guanfacine, while resembling those of clonidine, were generally weaker than those of clonidine.View full abstractDownload PDF (9120K)
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