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Biomedical subjects

M Misawa

Publications and source records attributed to M Misawa.

At least 289 records · Page 16Linked to original sources
PubMed1982

[Effects of methanobenzazonine (2,3,4,5,6,7-hexahydro-1,6-methano-1H-4-benzazonine) derivatives on the cough reflex and respiration].

Antitussive and respiratory effects of three newly synthesized methanobenzazonine derivatives and their d- and l-isomers were investigated to understand the relationship between the cough and respiratory centers. Antitussive effects were evaluated with the PEC (puncture electrode-induced cough) method in conscious d-, dl-, and l-ST-2123; d-, dl-, and l-ST-2121 into the right carotid artery at a dose range of 0.2-0.8 mg caused no effect on respiration. dl-ST-2121 at 0.4 to 0.8 mg and l-ST-2121 at 0.2 to 0.8 mg depressed respiration dose-dependently. Codeine (0.2-0.8 mg) depressed respiration slightly. Morphine (0.2-0.8 mg) depressed respiration more strongly. All the methanobenzazonine derivatives used, when given intraperitoneally, showed antitussive potencies that were 1/3-1/2 the potency of codeine. The antitussive potencies of the d-, dl-, and l-isomers of the three derivatives used were discussed on the bases of chemical structures and drug receptors. These results provide evidence of a discrepancy between the cough and respiratory centers in the brain stem.

Animals↗
PubMed1982

[Effects of respiratory drugs on the cough reflex].

In order to understand the relationship between the cough and respiratory centers in the brain stem, we investigated the effects of respiratory stimulants, pentylenetetrazol (PTZ) and nikethamide (NK), and a respiratory depressant, pentobarbital (PB)on the cough reflex. Coughs were induced in lightly anesthetized dogs by intraarterially into the vertebral artery. The rate (RR), amplitude (RA), and volume (RV) of the respiration and the number (NC) and amplitude (AC) of the cough reflex induced were used as indices. PTZ and NK, even at subthreshold doses for respiratory stimulation, enhanced the cough reflex (NC; not AC). On the other hand, PB at subthreshold doses for a respiratory depression decreased both NC and AC. The above findings suggest that respiratory stimulants generally enhance the cough reflex, and respiratory depressants reduce the cough reflex. Additionally, the thresholds for the cough responses to respiratory drugs are lower than those for the respiratory responses.

Animals↗
PubMed1981

Histamine receptors in the bronchial musculature and vasculature of the dog.

Participation of histamine H1- and H2-receptors in the bronchial musculature and vasculature of the dog was investigated by using the method for evaluating airway responses. A peristaltic pump and a Starling pneumatic resistance were used for a constant pressure perfusion. Dogs given 0.1 - 10 micrograms histamine by a close intraarterial injection showed increases in ventilation overflow (bronchoconstriction) and in blood flow (bronchial vasodilatation) in a dose-dependent manner. The bronchoconstriction produced by histamine was antagonized strongly by chlorpheniramine, a H1-receptor antagonist, but not modified by cimetidine, a H2-receptor antagonist. The bronchial vasodilation produced by histamine was antagonized by both chlorpheniramine and cimetidine. These results suggest that histamine evokes bronchoconstriction through H1-receptors and bronchial vasodilatation through H1- and H2-receptors.

Animals↗
PubMed1981

Effects of beta-adrenoceptor stimulants on the canine tracheal ciliated cells.

We investigated the effect of beta-adrenoceptor stimulants on the canine tracheal ciliated cells. A mucosal specimen of the tracheal membranous cell was placed in a chamber containing Hanks' solution. Membrane potential was recorded by an intracellular microelectrode, and ciliary beating was measured by a photoelectrical technique. Isoproterenol and salbutamol in 10(-7) to 10(-4) M caused a concentration-dependent increase in both frequencies of ciliary beating and small electrical oscillatories were superimposed on the membrane potential. Theophylline also increased frequencies of both activities in doses of 10(-5) M and above. Onset of action of theophylline was later than that of isoproterenol or salbutamol. All the above drugs only slightly depolarized the membrane potential, in concentrations of 10(-4) M. Propranolol (10(-7)-10(-4) M) alone had little effect on ciliary beating and electrical activity. However, the effects of isoproterenol and salbutamol were effectively antagonized by propranolol (10(-5) M). Dibutyryl cyclic AMP (10(-7)-10(-4) M) caused concentration-dependent increases in ciliary beating and electrical activity. These results suggest that potent bronchodilators such as beta-stimulants and theophylline increase the activity of tracheal ciliated cells by stimulating the intracellular cyclic AMP system.

Adrenergic beta-Agonists↗
PubMed1981

Effects of expectorants on the canine tracheal ciliated cells.

Many expectorants are clinically effective as they reduce viscosity and facilitate expectoration. There are, however, few reports on effects of expectorants on tracheal ciliated cells. We investigated the effects of N-acetylcysteine, ethylcysteine and bromhexine on the ciliary activities of the canine trachea. Ciliary movement was estimated using a phototransistor, and intracellular electrical activity was measured with a microelectrode method, in vitro. N-Acetylcysteine, ethylcysteine and bromhexine in low concentrations under a low perfusion rate (0.1 ml/min) produced an increase in the amplitude and frequency of ciliary beating, while N-acetylcysteine and ethylcysteine caused a cilio-depression in high concentration. N-Acetylcysteine, ethylcysteine and bromhexine, under a low perfusion rate, did not affect the intracellular electrical activity. On the other hand, these three drugs under a high perfusion rate (1 ml/min) produced no change in the ciliary movement and the intracellular electrical activity in concentrations of 10(-8)-10(-4) M. These results suggest that the increase in ciliary activity produced by the mucolytic drugs is not due to a direct effect on the ciliated cells, but rather to a mucolytic effect on the mucus around the cilia.

Acetylcholine↗
PubMed1981

[Histological and histochemical changes of tracheal secretory cells following bromhexine treatment (author's transl)].

The effects of bromhexine, a mucolytic agent, on secretory activities of canine tracheal secretory cells and on behaviour of glycoprotein in these secretory cells were investigated histologically and histochemically. Following bromhexine treatment, the number of total glycoprotein-containing goblet cells (GC) remained the same. The number of acid glycoprotein (AGP)-containing GC was reduced concentration-dependently, while neutral glycoprotein (NGP)-containing GC significantly increased with doses of 10-6, 10-5 and 10-4M. The number of sulphated glycoprotein (SGP) in AGP-containing GC decreased concentration-dependently. Acinar inner diameter of the submucosal gland and an acinar inner diameter of this gland to wall ratio (AIWR) increased with doses of 10-5 and 10-4M. Particularly, AIWR significantly increased with dose of 10-4M. Thickness of the acinus tended to slightly decrease concentration-dependently. AGP content in glandular cells decreased, while NGP content in these cells markedly increased, concentration-dependently. SGP content in the glandular cells decreased. Total saccharide and protein concentrations in the incubation fluid significantly increased with higher concentrations of the treatment, whereas N-acetylhexosamine slightly decreased concentration-dependently. These findings suggest that bromhexine does not enhance secretory activities of GC, but does stimulate the activities of the submucosal glands, when the drug is given in higher concentrations. Bromhexine markedly dissolves AGP in granules of the secretory cells.

Animals↗
PubMed1981

[Effect of bromhexine on the tracheal secretory cells with enhanced mucus synthesis by pilocarpine treatment (author's transl)].

The effects of bromhexine on secretory activities of canine tracheal secretory cells with stimulated synthesis of acid glycoprotein (AGP) by pilocarpine 10(-6)M treatment an on behaviour of glycoprotein in these secretory cells were investigated histologically and histochemically. Following bromhexine treatment, the number of total glycoprotein-containing goblet cells (GC) remained unchanged. The numbers of AGP-containing and sulphated glycoprotein (SGP)-containing GC significantly decreased, while neutral glycoprotein (NGP)-containing GC significantly increased. The acinar inner diameter of the submucosal gland and the acinar inner diameter of this gland to wall ratio slightly increased. Thickness of the acinus and Reid index slightly decreased, concentration-dependently. AGP and SGP content in glandular cells decreased, while NGP content in these cells markedly increased. Bromhexine 10(-5) and 10(-4)M treatment resulted in increased total saccharide and protein concentrations in the incubation fluid, whereas the agent significantly decreased N-acetylhexosamine, in a concentration-dependent manner. These findings suggest that while bromhexine does not stimulate secretory activities of GC, it does slightly stimulate the activities of the submucosal glands. Bromhexine markedly dissolves AGP in the granules of these secretory cells.

Animals↗
PubMed1981

[Reflex effects of cough reflex on the tracheobronchial vascular tone (author's transl)].

In a previous paper, it was shown that the cough reflex was accompanied by a slight fall of systemic arterial pressure, tracheal constriction and tracheal vasodilation. In the present study, tracheobronchial muscular and vascular tones during the cough reflex were investigated using the blood perfused canine tracheal and bronchial preparations in situ. The cough reflex was elicited with electrical stimulation of the membraneous wall mucosa of the upper trachea. In the blood perfused tracheal preparation, a close intraarterial injection of atropine or bilateral vagotomy inhibited the tracheoconstriction but had no effect on the tracheal vasodilation during the cough reflex. In the blood perfused bronchial preparation, electrical stimulation of the upper tracheal mucosa induced bronchial constriction but not bronchial vasodilation. Lung inflation with air resulted in a bronchial vasodilation and which persisted even after a close intraarterial infusion of atropine and benzonatate and after bilateral vagotomy. These findings indicate that the tracheobronchial constriction response are primary reflex effects following coughing and the tracheobronchial vasodilation responses are secondary reflex effects induced by increase in internal pressure of the respiratory tract.

Animals↗
PubMed1980

Continuous determination of tracheobronchial secretory activity in dogs.

We have designed a new method for continuous recording of the output of respiratory tract fluid, the approach representing a modification and combination of the intratracheal electrode and stopper methods which we had employed originally. Electrical resistance change indicated alteration in the output of respiratory tract fluid, without alteration in composition and temperature of fluid, tracheal muscular tone or respiratory movement, at least, within a physiological range. Among the expectorant drugs thus tested, pilocarpine, 100 and 200 micrigrams/kg given intravenously, significantly and in a dose dependent manner augmented the output of the fluid about 5 minutes after the administration. Given orally in a dose of 2 mg/kg, the output of fluid increased in about 20 minutes. Senega syrup, 0.3 ml/kg had no effect when given intravenously, yet, 2 ml/kg given orally increased the output of fluid within 5 minutes, thereby suggesting that the related secretagogic activity is due to a reflex action following stimulation of the gastric mucosa. Emetine, 2 mg/kg given orally increased the output about 20 minutes after administration while glyceryl guaiacolate, 50 mg/kg had no effect. We propose that our method be used to evaluate expectorants for clinical use as the continuous monitoring of the output of respiratory tract fluid apparently provides a more accurate assessment.

Animals↗
PubMed1980

[Effects of peripheral airway response on the cough reflex (author's transl)].

The modification of cough reflex by contraction and relaxation of the peripheral airway was investigated in anesthetized dogs. For administration of the drugs directly into the peripheral airway, an arterial cannula was chronically implanted in the right bronchial artery via the right intercostal artery. The cough reflex was induced by electrical stimulation of the upper tracheal mucosa by means of an electrode-cannula. Evaluation of the cough response was made by changes in frequency and amplitude of coughs. Drug solutions were infused for 5 min at a rate of 0.17 ml/min into the right bronchial artery. Intraarterial infusion of isoproterenol, 1-3 mu g/min, reduced the amplitude, but had no effect on the frequency of coughs, while that of histamine, 3-10 mu g/min, increased the frequency and amplitude of coughs. Atropine, 100 mu g/min, caused no significant changes in amplitude and frequency, respectively. Benzonatate, 0.85 mg/min, reduced the frequency, but had no effect on the amplitude. Thus, the tonus of the peripheral airway, in particular the airway contraction, may the increase the frequency of cough reflex by lowering the threshold of the airway receptors.

Airway Resistance↗
PubMed1975

Broad-specificity proteinase inhibitors in Scopolia japonica (Solanaceae) cultured cells. Isolation, physicochemical properties, and inhibition kinetics.

Proteinase inhibitors were isolated from Scopolia japonica cultured cells. Isolation procedures involve concentration by a hydrophobic resin of Diaion HP-20, decolorization by Duolite A-7, affinity chromatography on trypsin-Sepharose, and Bio-Gel P-4 chromatography. It was found that the proteinase inhibitors from S. japonica cells are a mixture of at least five components. For the inhibitory components except one, amino acid analyses, measurements of sedimentation equilibrium and optical rotatory dispersion (ORD) were carried out. The inhibitors were shown to be the polypeptides with molecular weights in the range of approximately 4000 to 6000. In addition, one of them was found to have approximately 15% alpha-helical conformation by the Moffitt-Yang analysis of ORD data. The inhibitors were found to have potent inhibitory activity for trypsin, chymotrypsin, plasmin, kallikrein and pepsin but not for papain with synthetic and natural substrates. These inhibitors formed stable complexes with trypsin and chymotrypsin in an equimolar ratio, and their inhibitory mechanisms for both enzymes were of non-competitive type.

Amino Acids↗
PubMed1975

Production of plant virus inhibitor by Phytolacca americana suspension culture.

The inhibitory activity of tobacco mosaic virus (TMV) infection was assayed with the extracts of various callus tissues derived from the intact plants. Phytolacca americana callus was selected as a producer of the virus inhibitor and its cultural conditions in suspension were examined for cell growth and the inhibitor production. A modified liquid medium containing twofold concentrations of all components in that of Murashige and Skoog plus2,4-D (1.0 mg/liter) and sucrose (6%), but without any vitamins and glycine was chosen for production of higher levels of the inhibitor. TMV infections in tobacco, bean, and tomato plants were markedly inhibited by the introduction of the disrupted whole broth of suspension cultured P. americana.

Antiviral Agents↗