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Biomedical subjects

M Hojo

Publications and source records attributed to M Hojo.

At least 91 records · Page 5Linked to original sources

Two-dimensional Doppler echocardiographic assessment of closure of the ductus arteriosus in normal newborn infants.

To elucidate the mechanism involved in closure of the ductus arteriosus (DA), 50 normal full-term infants were examined with two-dimensional and pulsed Doppler echocardiography. The examinations were performed initially within 1 hour after delivery and serially for 3 days. The two-dimensionally derived long-axis plane of the DA disclosed a characteristic localized protrusion into its lumen in 30% of the subjects within 1 hour, in 80% by 4 hours, in 96% by 8 hours, and in all by 24 hours after birth. In 10 infants in whom the intraluminal protrusion did not appear within 4 hours after birth, none had any recognizable changes in the inner diameter or length of the DA during this initial period. The development of the intraluminal protrusion resulted in localized narrowing of the ductal lumen. Doppler echocardiography revealed a high-velocity jet within and downstream from the narrowed portion of the DA. Thereafter, ductal narrowing progressed along the entire length. The intraluminal protrusion may be early evidence of ductal changes leading to eventual functional and anatomic closure.

Age Factors↗

[2 cases of bullous pemphigoid and Bowen's disease associated with esophageal cancer].

There are many published reports on the combination of malignant tumors of the digestive tract and various skin diseases. To date, 8 cases with combined bullous pemphigoid and malignant tumor, or Bowen's disease and malignant tumor, have been reported in Japan. In only 2 cases was the esophageal cancer combined with skin disease. The pathophysiological relationship between skin diseases and malignant tumors of the digestive tract remains unknown.

Aged↗

[Effects of guanabenz on the cardiovascular system, in comparison with clonidine and guanethidine].

Cardiovascular actions of guanabenz, a new antihypertensive agent, were studied in comparison with those of clonidine and guanethidine. Guanabenz, administered intravenously, produced a rise of blood pressure which was followed by a prolonged fall in anesthetized dogs. Guanabenz also decreased the heart rate, inhibited the respiration, and produced an alteration in T wave and a prolongation of PQ or TP interval in the ECG of the dog. Such effects of guanabenz on blood pressure and heart rate were observed in the cat, rabbit and rat, but there was a slight species-difference in the effects. Clonidine, but not guanethidine, produced responses similar to those of guanabenz. The potency of guanabenz to produce hypotension and bradycardia was approximately 1/10 that of clonidine and 10 times higher than that of guanethidine. The depressor effect of guanabenz was not observed in the spinal cats; thus, the blood pressure rose after the administration. When guanabenz was administered intracerebroventricularly or into the nucleus tractus solitarius of rats, the initial pressor response was not produced, and the depressor and bradycardiac responses were observed. Guanabenz, administered intravenously or intra-arterially, produced an inhibition of cardiac functions, decreased the blood flow of common carotid and femoral arteries, and elevated the perfusion-pressure of the hindlimb in the dog. In the isolated rabbit and guinea-pig atria, guanabenz produced negative inotropic and chronotropic effects and attenuated the rate of rise of the action potential. The contractile responses to serotonin and histamine in the isolated rabbit thoracic aorta were noncompetitively inhibited by guanabenz. From these results, it is suggested that the hypotensive and bradycardiac actions of guanabenz are mediated via central actions, as well as those of clonidine. Furthermore, in addition to the central actions, it was found that guanabenz acts directly on cardiovascular tissues and attenuates the responsiveness.

Animals↗

[Pharmacological studies of guanabenz. Effects on the peripheral nervous and other organ systems].

General pharmacological properties of guanabenz (GUB), a new anti-hypertensive agent, were studied in comparison with those of clonidine (CLD) and guanethidine (GUD). Intravenous or peroral administration of GUB caused a contraction of the nictitating membrane in cats and mydriasis in mice, while it produced an inhibitions of the gastrointestinal motility in dogs; the motility of isolated rabbit ileum; and chacol transport, salivation and gastric acid secretion in rats. GUB had no or slight inhibitory actions on contractile responses induced by peripheral sympathetic or parasympathetic nerve stimulation in various organs; however, it had antagonistic actions against the norepinephrine-induced contraction of isolated guinea-pig vas deferens. The contractile responses to epinephrine and tyramine in the nictitating membrane and to sympathetic nerve stimulation in isolated guinea-pig vas deferens were potentiated by GUB. GUB specifically antagonized the serotonin-induced contraction of the isolated rat fundus strip and nonspecifically inhibited acetylcholine, histamine or Ba2+-induced contractions of isolated guinea-pig ileum at higher concentrations. GUB exhibited local anesthetic actions and diuretic effects, but had no particular actions on neuromuscular transmission, isolated rat uterus, guinea-pig tracheal muscle and the hematic system. These effects of GUB were found to be almost identical with but less potent than those of CLD. The effects of GUD were basically different from GUB.

Animals↗

[Pharmacological study of mequitazine (LM-209) (II). Anti-allergic action (author's transl)].

The anti-allergic effect of Mequitazine (LM-209) which was found to have an anti-histaminic activity was investigated in guinea-pigs. The inhibitory activities of LM-209 on the Schultz-Dale reaction and ileum contraction by some mediators released from the sensitized guinea-pig lung were the same as those of clemastine fumarate (CL) but with 5 times the potency. LM-209 and CL, but these activities were less potent than in the case of disodium cromoglycate. The various anaphylactic reactions mediated by IgG in guinea-pigs were inhibited by LM-209, CL and chlorpheniramine maleate (CPM). The homologous PCA mediated IgE in rats was also inhibited by LM-209, CL and CPM, but the duration of the action with LM-209 was markedly longer. In experimentally-induced asthma, the decrease of respiratory rate and volume was significantly inhibited by LM-209, but was not affected by CL. Thus, LM-209 seems to inhibit the allergic reaction mainly by an antagonistic action on allergic mediators.

Anaphylaxis↗

[Pharmacological study of mequitazine (LM-209). (IV). General pharmacological action (author's transl)].

The general pharmacological actions of LM-209 were studied in rats, cats, dogs, guinea pigs and mice and the findings were compared with data on clemastine fumarate (CL). LM-209 but not CL produced a slight increase in pulse pressure and tachycardia. Inhibitory effects of LM-209 against contraction of the vas deferens and nictitating membrane, mainly dominated by sympathetic innervation, were remarkably less potent than CL. Inhibitory effects of LM-209 in the gastrointestinal tract were slightly more potent than CL. LM-209 accelerated norepinephrine-induced pressor reaction, while CL inhibited these effects at the dose level inhibiting histamine-induced depressor reaction. At the oral dose level showing anti-histaminic and anti-allergic actions, LM-209 but not CL had slight anti-tussive action, in an experimental model. Local anesthetic action of LM-209 was slightly more potent than that of lidocaine. LM-209 showed the same properties and potencies as CL, in most of the general pharmacological experiments.

Animals↗

[Pharmacological study of mequitazine (LM-209) (III). Action on the central nervous system (author's transl)].

The action of an anti-histaminic agent, Mequitazine (LM-209) on the central nervous system was investigated. We found that LM-209 did not affect the spontaneous and co-operative movement in mice, did not induce muscle relaxation, analgesic effects or anti-convulsant effect in micr or hypothermic effects in rats. The anti-oxotremorine effect of LM-209 in mice was about 10 times more potent than clemastine fumarate (CL) and the same as promethazine. The activity and duration of the action were also superior to diethazine and orphenadrine used as an anti-Parkinson drug. LM-209 prolonged by 50% the hypnotic time induced by hexobarbital at 50 mg/kg (p.o.) in mice, while CL prolonged 50 and 100% it at 25 and 50 mg/kg (p.o.) respectively. In the EEG of rabbits, LM-209 produced a resting pattern, inhibited the arousal responses and recruiting responses and the effect was the same as CL and less potent than promethazine. From these results, the activity of LM-209 on the central nervous system (except for the anti-oxotremorine effect) seems to be the same as or somewhat less potent than CL. Therefore LM-209 should be an effective and anti-histaminic agent for clinical application.

Analgesics↗

[Pharmacological study of mequitazine (LM-209) (I). Antagonistic actions of chemical mediators (author's transl)].

Antagonistic activities of Mequitazine (LM-209) on chemical mediators and in particular histamine were investigated in guinea-pigs, mice and rats. The antagonistic activity of LM-209 for histamine in the isolated ileum and trachea of guinea-pigs was less potent than that for clemastine fumarate (CL) and chlorpheniramine maleate (CPM) while that for acetylcholine was more potent than CL and CPM. Moreover, the antagonistic activities of these three compounds on serotonin and bradykinin were almost equipotent in the excised ileum. Using a modified Konzett-Rössler method, the bronchodilating effect of LM-209 (p.o.) for histamine was same as CL, but that for acetylcholine was more potent than CL and CPM. The protective activity of LM-209 (p.o.) on acute death induced by histamine and metacholine in mice was the same as CL, but the duration of the anti-histaminic action was markedly longer than CL. LM-209 given orally inhibited markedly the increased vascular permeability by histamine in rats and the diarrhea by 5-HTP in mice, but did not affect on the histamine-induced ulcer in guinea-pigs. From these results, LM-209 appears to have potent and long acting antagonistic activity on various chemical mediators.

Acetylcholine↗

[Pharmacological study of Mequitazine (LM-209). (V). Pharmacological actions of a main metabolite of LM-209, mequitazine sulfoxide (LM-209 SO) (author's transl)].

The pharmacological action of a main metabolite of Mequitazine (LM-209), Mequitazine sulfoxide (LM-209 SO), was compared with data on LM-209 to investigate whether LM-209 is metabolized in vivo to the active form and if it has pharmacological actions. In the excised ileum of guinea-pigs, the anti-histaminic and anti-cholinergic activities of LM-209 SO were about 1/8 and 1/20, respectively, of LM-209. The protective activity of LM-209 SO on sudden death induced by histamine in mice was about 1/2.5 of LM-209. Acute toxicity of LM-209 SO given orally to mice was 1/3 of LM-209. In the EEG of rabbits, LM-209 SO did not affect the spontaneous pattern or the arousal and recruiting responses. The mydriatic and local anesthetic activities of LM-209 SO were significantly less than those of LM-209. Thus, the pharmacological activities and toxicity of LM-209 SO were significantly less potent than those of LM-209.

Animals↗

Modification by temperature of the response of isolated aorta to stimulatory agents and transmural stimulation.

Contractile responses of helically-cut strips of the rabbit aorta to drugs, ions and transmural electrical stimulation were compared at different temperatures of the bathing medium, the response at 37 degrees C being taken as control. The dose-response curve of norepinephrine was moved to the right and downward by lowering the temperature from 37 to 25 degrees C and by raising temperature to 40 degrees C. Responses to transmural neural stimulation at frequencies of 5 and 20/sec were attenuated at 25 degrees C, the attenuation being greater in the response at the lower frequency. Concentrations of exogenous norepinephrine needed to produce the same magnitude of contraction as that with transmural stimulation were markedly increased by lowering the temperature to 25 degrees C. Contractile responses to norepinephrine (2 X 10(-6) M), histamine (2 X 10(-5) M) and angiotensin II (10(-7) M) were attenuated by 32-44% at 25 degrees C, whereas the responses to K+ (25 mM) and Ba++ (2 mM) were dependent on temperatures between 25 and 37 degrees C and were attenuated by 69 and 92%, respectively, at 25 degrees C. Contractures induced by Ca++ in K+-depolarized preparations exposed to Ca++-free media and also by Ba++ in preparations exposed to Ca++-free media varied directly by raising temperatures. Interference with the influx of divalent cations, such as Ca++ and Ba++, may be involved in the cold inhibition of aortic contractility.

Angiotensin II↗

Comparison of the relaxing effect of dopamine with that of adenosine, isoproterenol and acetylcholine in isolated canine coronary arteries.

Isolated canine coronary arteries were contracted with prostaglandin F2a and the relaxing effects of dopamine, adenosine, isoproterenol and acetylcholine were compared. Relaxation induced by dopamine in phenoxybenzamine-treated arteries was not significantly influenced by propranolol and atropine in concentrations sufficient to shift dose-respone curves of isoproterenol and acetylcholine, respectively, to the right. Dose-response curves of isoproterenol were shifted significantly to the left by 2 x 10(-5) M aminophylline. In contrast, the relaxing effect of adenosine was significantly attenuated by aminophylline (5 x 10(-6)-10(-4) M) in a dose-dependent manner. Kinetic analysis showed that aminophylline competitively antagonized the effect of adenosine, and the pA2 was 5.57. At these concentrations, aminophylline did not alter the relaxing action of dopamine and acetylcholine. It may be concluded that dopamine produces relaxation at a different site and with a different mechanism of action from those of isoproterenol, the effect of the latter being presumably mediated by cellular cyclic AMP, and that dopamine also does not share the site of action with adenosine and acetylcholine. It appears that receptive sites specific for adenosine are present in canine coronary arteries.

Acetylcholine↗