[At-home patient care of respiratory failure].
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Home Care Services↗
Biomedical subjects
M Egawa
Publications and source records attributed to M Egawa.
[General pharmacological action of 4-(o-benzylphenoxy)-N-methylamine hydrochloride (bifemelane hydrochloride, MCI-2016)--influence on the central nervous system].
General pharmacological action of 4-(o-Benzylphenoxy)-N-methylbutylamine hydrochloride (bifemelane hydrochloride, MCI-2016) was examined with regard to the effects mainly on the central nervous system. MCI-2016, at 30-100 mg/kg, p.o., only showed a weak sleep prolongation effect (mice), anti-convulsant action (mice) and a moderate facilitation of exploratory behavior, but produced no remarkable behavioral changes. Above the doses of 200 to 300 mg/kg, p.o., MCI-2016 produced a decrease in muscle or body tone, mydriasis and a slight decrease of locomotor activity. The drug, however, showed little influence on exploratory behavior, conditioned avoidance response and normal body temperature (rats). Normal body temperature in rabbits was also little affected by MCI-2016. Effects on EEG was characterized by moderate activation of spontaneous EEG and potentiation of arousal response by stimulation of the midbrain reticular formation (1.5-5 mg/kg, i.v.). The drug, however, did not significantly change the sleep-wakefulness cycle and REM-sleep in rats. MCI-2016 also showed little influence on spinal reflex potentials and neuromuscular junction at high doses (10 mg/kg, i.v.). These results may indicate that MCI-2016 has slight influence on overall behavioral and motor changes. Effects of MCI-2016 on acetic acid-induced writhing, carrageenin edema and corneal reflex were also examined. MCI-2016 showed moderate analgesic and anti-inflammatory actions at 50-100 mg/kg, p.o., and also showed local anesthetic action. The duration of local anesthetic action was relatively long but the drug produced no local damage.
Analgesics↗
[General pharmacological action of 4-(o-benzylphenoxy)-N-methylbutylamine hydrochloride (MCI-2016, bifemelane hydrochloride). Influence on respiratory and cardiovascular systems, renal function, autonomic nervous system, isolated smooth muscle and digestive organs].
MCI-2016 at 3 mg/kg, i.v., caused slight changes in systemic blood pressure (SBP), heart rate (HR), respiratory rate (RR) and ECG but at 10 mg/kg, i.v., it caused a significant increase in RR, decrease in SBP, increase or decrease in HR and a moderate change in ECG. Biphasic changes in SBP, HR and blood flow were sometimes observed after high doses. MCI-2016 also decreased SBP at 30 mg/kg, i.p., in SHR. MCI-2016 (50 mg/kg, p.o./day) showed little influence on SBP, HR and ECG in conscious beagle dogs. In isolated hearts, MCI-2016 decreased HR and contractility at the concentrations above 10(-5) g/ml, and 30 micrograms, i.a. MCI-2016 prolonged the AVCT at 10 mg/kg, i.v. MCI-2016 (i.v. or i.a.) moderately increased cerebral and femoral artery blood flows. MCI-2016 did not change CMRO2, but decreased MVO2. Coronary and renal artery flows were moderately increased by 10 mg/kg, i.v., of MCI-2016. Renal function was suppressed after 10 mg/kg, i.v., or 300 mg/kg, p.o., of MCI-2016. MCI-2016 potentiated the action of NE (increase in SBP, contractions of nictitating membrane and vas deferens), but showed little anti-cholinergic action. In contrast, MCI-2016 moderately increased gastrointestinal motility and salivatory response. As for the influence on isolated smooth muscles, MCI-2016 antagonized the contraction of blood vessels by high K+ at 10(-6) g/ml, or more, and it depressed the contractions by ACh, 5-HT, histamine and BaCl2 and also depressed spontaneous movements of uterus and ileum at 10(-5) M or more, in a nonspecific manner. MCI-2016 had no influence on liver damage and bile secretion, but inhibited stress ulcer and gastric acid secretion on the one hand, and caused gastric damage (125 mg/kg p.o., or more) on the other hand.
Animals↗
[General pharmacological action of tritoqualine (TRQ; (+/-)-(R*)-7-amino-4, 5, 6-triethoxy-3-[(R*)-5, 6, 7, 8-tetrahydro-4-methoxy-6-methyl-1, 3-dioxolo [4, 5-g] isoquinolin-5-yl] phthalide].
The general pharmacological action of TRQ was investigated, and the following results were obtained: With regard to its influence on the central nervous system, TRQ moderately potentiated the actions of hexobarbital (sleeping time) and methamphetamine (stereotyped behavior) at doses above 100 mg/kg, p.o. TRQ, however, had little influence on behavioral changes, EEG and motor function. TRQ only had slight influence on the respiratory and cardiovascular system at doses ranging from 0.1 to 3 mg/kg, i.v. Significant decrease in SBP and increases of HR, FAF and respiratory rate were observed after high doses (10-30 mg/kg, i.v.) of TRQ. TRQ also had little influence on contractility and pacemaker in isolated hearts, but moderately increased the coronary flow. The inhibitory effect of TRQ on the isolated smooth muscle was observed at high concentration and was non-specific. Furthermore, TRQ exhibited little influence on the autonomic nervous system. Among the effects of TRQ on the gastrointestinal system, it was shown that TRQ moderately increased the outflow of bile after doses above 1 mg/kg, i.v. TRQ also showed no remarkable actions on other aspects of the gastrointestinal system and blood coagulation system. Considering the present results, it may be suggested that there should be no serious problems in the application of TRQ as a hepatoprotective agent.
Animals↗
[Effects of hydrocortisone on function and structure of human skin fibroblasts in culture--especially effects on the growth, cytoskeleton and fibronectin].
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Cell Division↗
[Effect of MCI-2016 (bifemelane hydrochloride) on cerebral ischemia following ligation of both common carotid arteries in Mongolian gerbils].
Cerebral protective effect of MCI-2016 and influence of age on survival time in the cerebral ischemic model induced by bilateral-carotid-arterial ligation in male Mongolian gerbils were studied. Of all animals (6 to 40 weeks old), the mean survival time of the immature group (6 to 7 weeks) was long (3.6 hr), but variable, and that of the 10 to 40 weeks group was relatively stable (1.9-2.4 hr), but that of the older group (30-40 weeks) inclined to be reduced. Effects of drugs on this model were studied in 10 to 15 weeks old male Mongolian gerbils. The mean survival time in the control groups was 2.3-2.4 hr. After a single administration of MCI-2016 at doses of 25 mg/kg, i.p., and 100 mg/kg, p.o., the mean survival time were 8.1 and 6.4 hr, respectively. In these cases, some animals survived over 12 hr, while no animals surviving over 12 hr were observed in the control group. In this model, animals showed severe neurological symptoms. This, however, tended to be depressed by the administration of MCI-2016 at a dose of 25 mg/kg, i.p., which was observed early after ligation. A cerebral metabolic activator, Ca-hopantenate, slightly increased the survival time at a dose of 100 mg/kg, i.p., and a cerebral vasodilator, ifenprodil, was not effective. Subsequently, consecutive administration of MCI-2016 at a dose of 25 and 50 mg/kg, p.o., was more effective than a single administration of MCI-2016 at each dose. The mechanism for the cerebral protective effect of MCI-2016 was discussed.
Administration, Oral↗
[Effect of 4-(o-benzylphenoxy)-N-methylbutylamine hydrochloride (bifemelane hydrochloride, MCI-2016) on cerebral glucose metabolism].
To predict the influence of MCI-2016 on cerebral energy metabolism, the activity of MCI-2016 on uptake of 2-deoxy-D-[14C]glucose ([14C]-DG) into the brain under normal or hypoxic conditions, formation of 14CO2 from 14C-glucose in the brain, and local cerebral glucose utilization (LCGU) were examined. Cerebral uptake of [14C]-DG in mice were significantly enhanced by 6 day repeated administration of MCI-2016 (25 mg/kg, i.p.) and Ca-hopantenate (100 mg/kg, i.p.). The two drugs showed a slight enhancing effect on [14C]-DG uptake after single administration. As an index of cerebral glucose metabolism, 14CO2 formation from 14C-glucose was also stimulated by 6 day repeated administration of MCI-2016 (100 mg/kg, p.o., mice and rats) and Ca-hopantenate (250 mg/kg, i.p., rats). MCI-2016 moderately attenuated the decreased [14C]-DG uptake under the hypoxic condition in rats after 6 day repeated administration (100 mg/kg, p.o.). In addition, local cerebral glucose utilization (LCGU) in rats was also significantly potentiated by MCI-2016 (100 mg/kg, p.o., 6 days) in the areas of the visual cortex, thalamus ventral nucleus and uvula. From these results, MCI-2016 may be suggested to have a moderate activating effect on cerebral energy metabolism.
Administration, Oral↗
[Effects of 4-(o-benzylphenoxy)-N-methylbutylamine hydrochloride (MCI-2016, bifemelane hydrochloride) on spontaneous motor activity under different experimental conditions].
Effects of MCI-2016 on SMA changes were examined under several experimental conditions (normal conditions, hypoxia and head injury). Under normal conditions, MCI-2016 showed a significant increase of SMA after single administration of 12 mg/kg, i.p. Other doses (12.5-50 mg/kg, p.o. and 3-6 mg/kg, i.p.) of MCI-2016 were without significant effect. Under the same condition, MCI-2016 produced a dose-dependent increase of SMA after repeated doses of 12.5 to 50 mg/kg, p.o. (9-10 days administrations). After 5 days repeated administration, MCI-2016 significantly improved the decreased SMA due to hypoxia (rats) at 50 to 100 mg/kg, p.o. Furthermore, the drug also improved the decreased spontaneity due to head injury (mice) at 50 to 400 mg/kg, p.o. These improving effects of MCI-2016 were superior to those of Ca-hopantenate. The SMA increasing effect of MCI-2016 (12 mg/kg, i.p.) was antagonized more strongly by phenoxybenzamine than by haloperidol. In addition, the drug was shown to be rather antagonistic to the effects of anticholinergic agents. These effects may indicate the existence of qualitative differences between MCI-2016 and methamphetamine in the SMA increasing actions. It is also suggested that MCI-2016 may exhibit the above pharmacological effects through possible activation of noradrenergic and/or cholinergic mechanisms.
Animals↗
Effects of bifemelane hydrochloride (MCI-2016) on experimental amnesia (passive avoidance failure) in rodents.
To further predict the possible activity on memory disorders, the effect of MCI-2016 (bifemelane hydrochloride) was examined using the passive avoidance (PAR) failure technique as an experimental model of amnesia. The amnesia was produced either by post training treatments of electroconvulsive shock (ECS), scopolamine (mice) and cycloheximide or by pre-test injection of scopolamine (rats). In ECS-PAR failure model, the retention test was carried out 3 hr (3 hr experiment) or 24 hr (24 hr experiment) after ECS. MCI-2016 showed a significant improvement when administered just after ECS (3 hr experiment, 30 mg/kg, i.p.) or 0.5 hr before the retention test (24 hr experiment, 10-30 mg/kg, i.p.). Cahopantenate was only active in the 3 hr experiment (500 mg/kg, i.p.), and piracetam was rather active in the 24 hr experiment (60 mg/kg, i.p.). MCI-2016 (30 mg/kg, i.p.) prevented the scopolamine-induced PAR-failure. In this model, physostigmine (0.3 mg/kg, i.p.) exhibited a tendency to improve the failure. In another scopolamine-induced PAR failure model in mice, all of the test drugs showed a significant improvement at different dose levels. The effect of MCI-2016 (25-100 mg/kg, p.o.) was superior to those of piracetam, aniracetam and choline chloride. Higher doses of MCI-2016 were required to improve the cycloheximide-induced PAR failure. Considering the experimental conditions and results, it may be suggested that MCI-2016 ameliorates the amnesia possibly through its influence on memory consolidation and retrieval processes.
Animals↗
Effects of bifemelane hydrochloride (MCI-2016) on acetylcholine and norepinephrine release from cortical slices of bilaterally carotid-artery-ligated Mongolian gerbils.
Effects of bifemelane hydrochloride (MCI-2016) on acetylcholine (ACh) and norepinephrine (NE) release from cortical slices of bilaterally carotid-artery-ligated Mongolian gerbils were examined. ACh and NE release from cortical slices of Mongolian gerbils were increased 1 hr after the ligation of bilateral carotid arteries. Pretreatment of MCI-2016 (25 mg/kg, i.p.) attenuated the increase in the release of both neurotransmitters. These effects may participate in the protective effect of MCI-2016 on cerebral ischemia in Mongolian gerbils.
Acetylcholine↗
Effects of bifemelane hydrochloride (MCI-2016) on acetylcholine release from cortical and hippocampal slices of rats.
Bifemelane hydrochloride (MCI-2016) increased high K+-evoked acetylcholine (ACh) release from cortical and hippocampal slices of rats. The increasing effect of MCI-2016 was abolished in the absence of Ca ion and by pretreatment of reserpine (2.5 mg/kg, i.p.). These results suggest that monoaminergic neurons may be related to the enhancement of ACh release by MCI-2016. High K+-evoked ACh release from cortical slices was significantly decreased during aging. The decrease in ACh release was ameliorated by pretreatment of MCI-2016 (30 mg/kg, i.p.).
Acetylcholine↗
Increased triglyceride secretion rate and hyperinsulinaemia in ventromedial hypothalamic lesioned rats in vivo.
The present study aimed to measure triglyceride secretion rate (TGSR) into the circulation in ventromedial hypothalamic (VMH) lesioned rats. Average gain of body weight in VMH lesioned rats was 72 +/- 6 g (mean +/- SE, n = 9) in a week; significantly greater than that in controls (6 +/- 2, n = 8, P less than 0.001). TGSR was determined under hexobarbital anaesthesia in fasted rats by measuring the increase in plasma concentration after the triglyceride removal mechanism was blocked by injecting Triton WR-1339. TGSR in VMH lesioned rats was 500 +/- 37 mg/dl of plasma/h; markedly higher than that in controls (239 +/- 12, P less than 0.001). Serum insulin concentration in VMH lesioned rats was 2.26 +/- 0.32 ng/ml; significantly higher than that in controls (0.83 +/- 0.08, P less than 0.001). There was a positive correlation between serum insulin concentration and TGSR in VMH lesioned rats (r = 0.709, P less than 0.05). The increased secretion rate of triglyceride in VMH lesioned rats is discussed in connection with the development of obesity in these rats.
Animals↗
[The activating effect of MCI-2016 (bifemelane hydrochloride) on EEG in cats].
In order to make clear the activating effect of MCI-2016 on EEG, power spectrum analysis was performed and the interaction in EEG between MCI-2016 and some drugs were studied in succinylcholine-immobilized cats. MCI-2016 at doses of 5 and 10 mg/kg iv produced apparent arousal pattern in cortical EEG characterized by low amplitude fast wave, and evoked the right-shift in power spectrum. In the case of meclofenoxate at doses of 20 and 40 mg/kg iv, the shifts in power spectra were similar to that of MCI-2016, very slight changes were observed by Ca-hopantenate at a dose of 200 mg/kg iv and typical left-shift was introduced by imipramine at a dose of 2 mg/kg iv. MCI-2016 tended to suppress the SWS state induced by alpha-methyl-p-tyrosine and scopolamine at a dose of 350 mg/kg ip and 0.015 mg/kg iv, respectively. Subsequently, the duration of arousal state in EEG induced by physostigmine at a dose of 0.01 mg/kg iv was enhanced by MCI-2016 at a dose of 1.5 mg/kg iv whose injection does not produce any arousal pattern in EEG. The activating effect of MIC-2016 on EEG was indicated quantitatively and it is suggested that the cholinergic mechanism and the catecholaminergic mechanism would be involved in the EEG activating effect of MCI-2016.
Animals↗
Thyroid hormone unresponsiveness in two siblings with intrauterine growth retardation exophthalmos.
Two cases of a brother and a sister with thyroid hormone unresponsiveness are described. They had large goiters and high levels of thyroid hormones in the face of clinical euthyroidism. The birth weight of the brother was low for his gestational age. He was also lean and exophthalmic, as is often seen in Graves' disease.
Child↗
Substituted (omega-aminoalkoxy) stilbene derivatives as a new class of anticonvulsants.
A series of substituted (omega- aminoalkoxy )stilbene derivatives has been synthesized and screened for anticonvulsant activity. The effect of structural modification of these molecules on the activities has been systematically examined. Potent anticonvulsant activity was displayed by 2-[4-(4-methyl-1 piperazinyl)butoxy]stilbene (20) and some 2-[4-(3-alkoxy-1-piperidino)butoxy]stilbene derivatives (21, 37, 38, and 40), as determined by maximal electroshock seizure (MES) and pentylenetetrazol-induced convulsion tests in mice. Compound 21 exhibited more potent anti-MES activity than diphenylhydantoin and carbamazepine in further pharmacological tests in rats, and its therapeutic index was superior to those of two antiepileptic drugs.
Animals↗
Effects of ventromedial hypothalamic lesions on circadian rhythms in serum insulin, glucose, triglyceride and food intake in rats.
The effects of ventromedial hypothalamic (VMH) lesions on the circadian periodicity of serum insulin, glucose, triglyceride and food intake were studied in rats. The rhythms of serum insulin, glucose and triglyceride did not persist in VMH lesioned rats. The glucose level during the light period was reduced. The triglyceride and insulin levels were elevated. The VMH lesions markedly increased food intake during the later half part of the light cycle but kept it significantly less during the first half part. Thus, the VMH lesions abolished the circadian rhythmicity of serum insulin, glucose and triglyceride and attenuated the rhythmicity of eating through increase in daytime consumption.
Animals↗
Effects of 4-(o-benzylphenoxy)-N-methylbutylamine hydrochloride (MCI-2016) on survival time and brain monoamine levels in bilaterally carotid-artery-ligated gerbils.
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Animals↗
Inhibition of in vitro neutrophil responses to chemotactic factors by piroxicam.
The effect of piroxicam on polymorphonuclear neutrophils (PMN) functions induced by several stimuli was evaluated in vitro. Preincubation of rabbit or human PMN with piroxicam inhibited the cellular responses elicited by N-formyl-methionyl-leucyl-phenylalanine (FMLP) such as superoxide anion (O2-) generation, granule enzyme release and chemotaxis. The effectiveness of piroxicam on each response was superior to those of indomethacin and ibuprofen. Also when either concanavalin A, zymosan-treated serum or ionophore A23187 was used as stimuli, piroxicam inhibited O2- generation of PMN. The inhibitory effect of piroxicam on FMLP-induced O2- generation was dependent on the concentration of stimuli and was reversed by increasing the extracellular calcium concentration. In addition, piroxicam had no effect on the activity of a chymotrypsin-like esterase, N-acetyl-phenylalanine-beta-naphthyl esterase, isolated from rabbit PMN. These results suggest that at least some of the anti-inflammatory effects of piroxicam may be mediated by affecting PMN functions, and the inhibition of O2- generation of PMN by piroxicam may be related to its capacity to modulate the association of calcium with these cells.
Animals↗