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Biomedical subjects

M Misawa

Publications and source records attributed to M Misawa.

At least 253 records · Page 14Linked to original sources
PubMed1987

Effects of mast cell stabilizers on a new bronchial asthma model using compound 48/80 in dogs.

Development of a nonimmunologically induced experimental asthma model using compound 48/80 was attempted. Male mongrel dogs anesthetized with pentobarbital-Na were immobilized with decamethonium bromide under artificial respiration. Airway resistance was measured with a modified Konzett-Rössler method and expressed as a change in ventilation overflow (VO). Inhalation of compound 48/80 caused no change in VO even in high concentrations up to a 1% solution. Infusion of compound 48/80 into the bronchial artery at a dose of 0.2 mg/min for 10 min by using the right bronchial perfusion method caused a marked increase in VO accompanied by decreases in perfusion pressure and systemic blood pressure. The compound 48/80-induced bronchoconstriction was inhibited 58% by surgical vagotomy and was almost abolished by chlorpheniramine (10 mg/kg, intraduodenally (i.d.)). Disodium cromoglycate (inhalation of 1% solution along with 5 mg/kg, i.v.), tranilast (300 mg/kg, i.d.) and NCO-650, a new antiallergic drug (100 mg/kg, i.d.) significantly inhibited the compound 48/80-induced bronchoconstriction. These results indicate that compound 48/80 infusion into the bronchial artery produces an asthma-like bronchoconstriction, the main chemical mediator involved in this response would be histamine acting through H1-receptors, and effects of mast cell stabilizers can be evaluated with this model.

Airway Resistance↗
PubMed1987

Strain difference in an allergic asthma model in rats.

A new rat asthma model was devised, and with the model, allergic bronchoconstrictor responses and effects of disodium cromoglycate (DSCG) were compared among Wistar, Lewis and Fischer 344 rats. Rats were actively sensitized with DNP-Ascaris antigen (DNP-As) and killed Bordetella pertussis vaccine. After eight days, asthmatic response was provoked by inhalation of DNP-As. The bronchomotor response was measured with a modified Konzett-Rössler method in diaphragm-sectioned rats. The inhalation of DNP-As using a newly devised apparatus caused a marked asthmatic response with negligible effects on systemic blood pressure and heart rate. The extent of the bronchoconstriction provoked was of the following order: Wistar greater than Lewis = Fischer 344. There was no relationship between the individual 48 hr PCA titer and the bronchoconstriction that occurred in any strain of rats. The bronchoconstrictions were inhibited by DSCG (10 mg/kg, i.v.) and the inhibition ratios were 28%, 36% and 33% in Wistar, Lewis and Fischer 344 rats, respectively. The inhibitions were statistically significant in the latter two strains. Fischer 344 rats were more susceptible to the damage resulting from the operative procedures. The above findings suggest that Lewis rats are the most suitable among the above strains as a model for studying the effects of antiallergic agents.

Animals↗
PubMed1987

[Changes in CNS catecholamine levels in tolerance to morphine-induced central excitation in mice].

Effects of a morphine single injection on catecholaminergic system in the brain were studied in mice treated with morphine-admixed food (MAF). The ambulatory activity was determined with the tilting cage method for 60 min after single morphine injection (10 mg/kg s.c.). After measurement of the ambulatory activity, mice were sacrificed and each brain was dissected out. Catecholamine levels were determined by HPLC-ECD system. Tolerance to morphine-induced ambulatory activity was developed by MAF (2 mg/g food) treatment for 5 days. The activating effect of a single morphine injection on dopamine metabolic rate in striatum and cortex in naive mice was reduced by MAF treatment. In midbrain and hippocampus, there was no influence of MAF treatment on the activation of dopaminergic neurons. It is suggested that dopaminergic neurons in striatum and cortex were hardly activated by morphine injection in MAF-treated mice, which might lead to tolerance to morphine-induced ambulatory activation.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1986

[Antitussive and expectorant effects of Asada-ame extract].

Asada-ame containing Platycodi Radix, Ginseng Radix, Ephedrae Herba and Ipecacuanhae Radix extracts has been hitherto widely used as an antitussive and expectorant. In the present study, the antitussive effect and tracheo-bronchial secretory activity of Asada-ame extract (AE) were investigated with laboratory animals. Antitussive effect was evaluated with the puncture electrode-induced cough method in conscious guinea pigs. AE showed a significant antitussive effect which lasted more than one hr. 50% Antitussive doses were 76 mg/kg, i.p., and 500 mg/kg, p.o. Airway secretory effect was evaluated with the stopper method in anesthetized dogs. With oral administration of AE, the volume of respiratory tract fluid (RTF) increased, and viscosity of RTF, which was determined using the glass plate method, was decreased in a dose-dependent manner. The effects of AE on secretory activity of canine tracheal secretory cells were investigated in vitro with the histological/histochemical technique. With AE treatment, the thickness of the acini of submucosal glands was decreased, and the ratio of acinar inner diameter of the gland to tracheal wall was increased. Furthermore, the number of acid glycoprotein-containing submucosal glandular cells was decreased by AE, suggesting a mucolytic effect of AE. The above findings indicate that AE has significant antitussive and expectorant effects.

Animals↗
PubMed1986

Effects of the new antiallergic drug 11-oxo-11H-pyrido[2,1-b] quinazoline-2-carboxylic acid on bronchial and cutaneous allergic responses to ascaris in dogs.

The effects of 11-oxo-11H-pyrido[2,1-b]quinazoline-2-carboxylic acid (Sm 857), a new antiallergic drug, on both bronchial asthma and active cutaneous anaphylaxis (ACA) reaction induced by Ascaris suum antigen in dogs were investigated. The airway resistance was determined using the modified Konzett-Rössler method. Sm 857 in doses of 30 and 100 mg/kg intraduodenally (i.d.) produced a remarkable inhibitory effect on the asthmatic bronchoconstriction induced by inhalation of Ascaris antigen in naturally sensitized dogs. Intravenous administration of Sm 857 (10 mg/kg) also strongly inhibited the Ascaris-induced bronchial asthma. Sm 857 had a more powerful antiasthmatic activity than tranilast. In ACA reactions, 10 dilutions of Ascaris extract and histamine were injected intradermally to dogs and each wheal provoked was determined. Sm 857 (100 and 300 mg/kg i.d.) had little or no inhibitory effect on the antigen-induced wheals, while tranilast only in a high dose (300 mg/kg i.d.) showed an inhibitory effect. Chlorpheniramine (10 mg/kg i.d.) prevented the ACA reaction completely. Sm 857 thus appeared to have no antihistaminic effect. Above findings suggest that Sm 857 may be useful for the treatment of bronchial asthma as an orally active drug, exerting its action probably through a mast cell stabilizing effect.

Animals↗
PubMed1986

Ultrastructural and enzyme histochemical studies in orotic acid-induced fatty liver.

To confirm the relationship between fatty changes and zonal distribution in the hepatic lobules, we studied the ultrastructural and enzyme histochemical alterations in rat hepatocytes of orotic acid which blocks the release of lipoproteins, administered for 7 days, fatty changes were clearly detected in the hepatocytes, but no zonal distribution of fat in the hepatic lobules was detected. The most striking ultrastructural alterations were observed in the rough endoplasmic reticulum and Golgi complexes. The intensity of the staining of non-specific esterase and lipase was markedly decreased. Based on these data, functional aspects of the hepatocytes in orotic acid administration were discussed.

Animals↗
PubMed1985

Attenuation of aspirin analgesia by calcium loading in healthy subjects.

To clarify the mechanism of aspirin analgesia, the relationship among analgesic and hypocalcemic effects and pharmacokinetics of aspirin was investigated in 20 healthy subjects at 20-23 years old. Four experimental groups were made, that is, (1) aspirin 1.0 g, (2) aspirin 1.0 g + calcium gluconate 1.5 g X 2, (3) calcium gluconate 1.5 g X 2, (4) control (placebo). Calcium gluconate was administered orally twice, that is, 30 and 90 min after oral administration of aspirin. The experiments were carried out under a double blind method. As an analgesic test, the ultrasonic method was used. Aspirin (1.0 g) caused a significant analgesia, the effect reaching the maximum at 90 min and prolonging for about 3 h. Simultaneously, plasma calcium level significantly decreased and kept going down, at least, until 180 min after administration of aspirin. However, when calcium gluconate was loaded at 30 and 90 min after administration of aspirin, both the analgesic and hypocalcemic effects of aspirin were significantly inhibited. The plasma aspirin concentration reached a maximum 30-60 min after administration of aspirin in both groups: aspirin alone and aspirin with calcium gluconate. On the other hand, plasma salicylic acid concentration kept increasing up to 180 min after administration of aspirin in either group. The plasma aspirin and salicylic acid levels in both groups were similar.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1985

Effects of bromhexine on the secretions of saliva and tears.

Effects of bromhexine and pilocarpine on the secretions of submaxillary saliva in dogs and of tears in rabbits were investigated including their effects on lysozyme activity in an attempt to elucidate the efficacy of bromhexine on Sjögren's syndrome. Pilocarpine (0.3 mg/kg, p.o.) significantly increased spontaneous salivary flow rate, but bromhexine (20 and 40 mg/kg, p.o.) had almost no influence on spontaneous salivary flow rate. Pilocarpine increased total protein, saccharide, lysozyme and IgA secretions in saliva under electrical stimulation of the chorda tympani. Bromhexine did more markedly increase total lysozyme and IgA secretions in saliva, with minor increases in total protein and saccharide secretions. Pilocarpine (0.4 mg/kg, i.v.) had almost no influence on lysozyme concentration in tears, whereas it markedly increased tear secretion volume leading to an increase in total lysozyme secretion. On the other hand, bromhexine (4 and 8 mg/kg, i.v.) significantly increased both lysozyme concentration and total lysozyme secretion in tears from 50 min after injection, without influencing tear secretion volume. From these findings, it is suggested that bromhexine may work effectively on Sjögren's syndrome by acting to accelerate the secretions of lysozyme and IgA in saliva and tears, which are known to have antiinflammatory and bacteriocidal effects.

Animals↗
PubMed1984

Antitussive effect of RU-20201--central and peripheral actions.

The antitussive effect of the new compound 1, 2, 3, 4a, 9b-hexahydro-8, 9b-dimethyl-4-[3-(4-methyl-piperazine-1-yl) propionamide] dibenzofuran-3-one dihydrochloride (RU-20201) was investigated in dogs and guinea pigs, including its sites of action. The antitussive effect of RU-20201 was about 1/10 as potent as that of codeine phosphate in dogs with the puncture electrode-induced cough (PEC) method and about 1/12 and 1/4 as potent as that of codeine phosphate in guinea pigs with the PEC and chemical stimulation methods, respectively. When RU-20201 was administered in a dose range of 1 to 10 mg into the vertebral artery toward the brain in lightly anesthetized dogs, no antitussive effect was observed against the coughing elicited by electrical stimulation of the central cut end of the superior laryngeal nerve. However, a stimulative effect on respiration, especially on respiratory rate occurred. The peripheral effect of RU-20201 on the cough was investigated using the in situ upper trachea perfusion preparation which allows a direct drug administration to the local site around the tracheal mucosa, this site being electrically stimulated to induce coughing. A close i.a. infusion of RU-20201 in doses of 1 and 3 mg/min into the tracheal vascular bed for 5 min inhibited the cough response elicited by mucosal stimulation. The above findings suggest that RU-20201 has a significant antitussive activity, the site of action being probably, at least, at the cough receptor level.

Animals↗
PubMed1984

The role of vagal reflex in mechanism of secretagogic action of bromhexine.

The in vivo effect of bromhexine on secretory activities of tracheal submucosal glands was investigated with a histological/histochemical technique with reference to a role of the vagal reflex. When bromhexine was given at 5, 10 or 20 mg/kg into the stomach of anesthetized dogs, the ratio of acinar inner diameter of the submucosal gland to wall thickness (AIWR) markedly increased in a biphasic manner; the early transient increase was seen 0.5 hr after administration, and the second prolonged increased occurred during 2 to 6 hr after administration. The early stimulant phase was almost abolished by atropine, 1 mg/kg i.v., or bilateral cervical vagotomy, whereas the second stimulant phase was not affected by these treatments. Emetine also induced a similar early increase in AIWR at 0.5 hr after administration, the change also being abolished by atropine or surgical vagotomy in this case. The number of submucosal glandular cells which stained blue and purple with a combination of alcian blue at pH 2.5 and periodic acid-Schiff was decreased by bromhexine, but the cell number which stained red was markedly increased. These histochemical changes in glandular cells were not influenced by treatment with atropine or surgical vagotomy. In the present study, it was found that bromhexine exerts both a secretagogic action on submucosal glands and a mucolytic action toward acid glycoproteins inside the cells in vivo. Also, the secretagogic action of bromhexine occurs biphasically; the first phase results from the vagal reflex probably through a gastrointestinal irritation, and the second phase results from a direct action on the glands.

Animals↗
PubMed1984

Analysis of the vagal reflex tracheal constriction in the dog.

We devised a preparation for measuring the vagal reflex tracheal constriction following the bronchoconstriction induced by histamine inhaled in the bronchial side in dogs. Properties of the vagal reflex tracheal constriction were investigated using this preparation. Histamine inhaled in the bronchial side caused the tracheal constriction following the bronchoconstriction. The tracheal constriction was inhibited by section of the bilateral superior laryngeal nerves or vagal cooling, respectively, but was not completely blocked. The combination of section of the bilateral superior laryngeal nerves and vagal cooling abolished the tracheal constriction. An i.v. administration of pentobarbital reduced both bronchoconstriction and tracheal constriction. These findings indicate that the tracheal constriction observed in the present study is mediated by the vagal reflex arc and that the extravagal pathway consisting of the recurrent and superior laryngeal nerves plays a role in a part of the afferent pathway of the vagal reflex airway responses. When the bronchoconstriction was completely abolished by isoproterenol inhaled in the bronchial side, the reflex tracheal constriction still existed. Transient inflation and deflation of the lungs caused reflex tracheal dilatation and constriction, respectively. We conclude that the vagal reflex airway constriction is due to complex effects which may be mediated by plural sensory receptors in the airways.

Animals↗
PubMed1984

[Changes in secretory activity of tracheal submucosal glands by repeated treatment with brovanexine and BR-227 in rats].

The effects of brovanexine (BvX) and BR-227 on sectetory activities of tracheal submucosal glands (SG) including behavior of mucus glycoproteins in the cells were investigated. BvX, BR-227 or bromhexine (BH) was given repeatedly at a dose of 10 or 20 mg/kg p.o. a day, to rats for 1, 3, 7 or 14 days. Then, the trachea was excised and drug effects were determined according to our histological/histochemical technique. The outer diameter of the acini of SG did not change, but the inner diameter markedly increased by the drug given for 3-14 days. The ratio of the acinar inner diameter to the tracheal wall thickness (AIWR) was increased with the 3, 7, and 14 day treatments with BvX or BR-227 at a dose of 10 mg/kg a day. On the other hand, these drugs at a dose of 20 mg/kg a day caused an increase in AIWR when drug was given for 1-14 days. BH (10 mg/kg a day)-induced increase in AIWR was shown when drug was administered for 7 and 14 days. The number of SG cells stained blue with alcian blue (pH 2.5)/periodic acid-Schiff decreased with the 1, 3, 7 and 14 day treatments, and a part of SG cells became red with the 7- and 14-day treatments. There was no significant difference in the effects among the three drugs both qualitatively and quantitatively. These findings indicate that repeated treatments with BvX and BR-227 have an effective secretagogic action on SG, and in addition, a mucolytic action toward acid glycoprotein in granules of the cells.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1984

[Effects of oxybutynin on the cardiovascular system in dogs].

The 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, accompanied 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 greater than oxybutynin greater than 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.

Acetylcholine↗