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Biomedical subjects

M Misawa

Publications and source records attributed to M Misawa.

At least 217 records · Page 12Linked to original sources
PubMed1990

Inhibitory modulation of the reflex tracheal constriction induced by afferent vagal stimulation.

Afferent cervical vagal electrical stimulation caused a reflex tracheal constriction. Atropine changed the tracheal constriction into a tracheal dilatation that was almost inhibited by propranolol. In the hypertonic trachea with 5-hydroxytryptamine, a reflex dilatation following a constriction was observed by afferent vagal stimulation. The reflex dilatation was inhibited about 50% by propranolol and was abolished by hexamethonium. These results suggest that the adrenergic and nonadrenergic inhibitory innervations may mediate the reflex tracheal dilatation, especially in a hypertonic tracheal condition.

Animals↗
PubMed1990

The effect of platelet-activating factor on histamine release from rat peritoneal mast cells.

The effect of platelet-activating factor (PAF) on histamine release from peritoneal mast cells of adult and young male rats was investigated. PAF alone tended to release histamine from the mast cells of adult and young rats, although very slightly. On the other hand, PAF significantly inhibited the histamine release induced by the Ca2+ ionophore A23187 in mast cells obtained from rats of either age group, but not that by compound 48/80. Such inhibition was not seen with lyso-PAF. CV-3988, a PAF antagonist, antagonized the inhibitory effect of PAF on the A23187-induced histamine release in mast cells from adult and young rats. These results suggest that PAF does not have a strong histamine-liberating action on mast cells, and that PAF inhibits the calcium influx into mast cells through the activation of PAF receptors.

Aging↗
PubMed1990

Platelet-activating factor (PAF)-induced rhinitis and involvement of PAF in allergic rhinitis in guinea pigs.

The effects of inhaled PAF on the guinea pig nasal mucosa were investigated. Intranasal pressure (INP) was recorded as an index of intranasal resistance. To access the capillary premeability of nasal mucosa, exudation of Evans blue into the nasal lavage fluid was determined. Inhalations of histamine and PAF markedly and significantly increased INP and dye exudation into the nasal cavities. The two responses to PAF were about 20-fold and 70-fold stronger than those of histamine, respectively. A PAF antagonist, CV-3988, significantly antagonized both the PAF-induced increases in INP and dye exudation. Indomethacin and OKY-046 had no effect on the PAF-induced responses. FPL-55712 inhibited the PAF-induced increases in INP and dye exudation by 52% and 40%, respectively. Ovalbumin (OA) antigen challenge by inhalation to sensitized guinea pigs resulted in significant increases in both INP and dye exudation. These two responses to 30 mg/ml OA were inhibited by CV-3988 (10 mg/kg, i.v.) by 55% and 40%, respectively. From the above results, it is indicated that: 1) inhalation of PAF evokes rhinitis-like symptoms through activation of PAF receptors, 2) the PAF-induced rhinitis is, in a part, mediated by leukotrienes, and 3) PAF might be involved in allergic rhinitis.

Animals↗
PubMed1990

[The effects of constituents of an antitussive and expectorant preparation on physical dependence on and antitussive activity of dihydrocodeine].

The effects of constituents of an antitussive and expectorant preparation on physical dependence potential and antitussive activity of dihydrocodeine (DC) were studied. Rats were treated with DC, methylephedrine (ME), chlorpheniramine (CP), and caffeine (CA) singly or simultaneously admixed with food (DC 0.125, ME: 0.25, CP: 0.05, CA: 0.25 mg /g of food) for 7 days. Subsequently, rats were treated with naloxone (0.5 mg/kg, sc) and withdrawal signs produced were observed. Naloxone-precipitated body weight loss in DC-treated rats was suppressed by simultaneous administration of the three drugs (ME, CP and CA) or CP, which is a H1-receptor antagonist. In abrupt withdrawal, the withdrawal signs were also suppressed by CP. Moreover, tripelennamine, the same kind of H1-receptor antagonist, suppressed naloxone-precipitated withdrawal signs, but cimetidine H2-receptor antagonist, did not suppress them. These results may suggest that H1-receptor antagonists suppress the development of physical dependence on DC, and that H1-receptors play an important role in the physical dependence. On the other hand, the cough reflex was induced by electric stimulation in order to evaluate the influence of ME, CP, and CA on antitussive effect of DC in guinea pigs. ME enhanced the effect of DC. These experimental findings suggest that the constituents of the antitussive and expectorant preparation suppress the development of physical dependence on DC, though they increase the antitussive effect of DC.

Animals↗
PubMed1990

[The effect of leukotriene C4/D4 receptor antagonist (ONO-1078) and thromboxane A2 synthetase inhibitor (OKY-046) on airway hyperresponsiveness induced by ozone exposure in guinea pigs].

To clarify the mechanisms of ozone-induced airway hyperresponsiveness, we studied the effect of leukotriene C4/D4 receptor antagonist (ONO-1078) and thromboxane A2 synthetase inhibitor (OKY-046) on airway hyperresponsiveness induced by ozone exposure in guinea pigs. Airway responsiveness to inhaled methacholine was determined in artificially ventilated guinea pigs using a modification of the Konzett-Rössler technique. After the methacholine challenge, bronchoalveolar lavage (BAL) was performed. After 1 hour following ozone exposure (2.9 ppm, 30 min), airway responsiveness increased significantly. There was no cellular change in the bronchoalveolar lavage fluid (BALF). Pretreatment with ONO-1078 (30 mg/kg, i.p.) or OKY-046 (20 mg/kg, i.p.) caused no effect on airway responsiveness before ozone exposure, and inhibited the increase of airway responsiveness induced by ozone exposure. These results suggest that leukotriene and thromboxane play an important role in the development of airway hyperresponsiveness induced by ozone exposure in guinea pigs.

Acrylates↗
PubMed1990

[Bone marrow transplantation for MDS].

Five patients with myelodysplastic syndrome (RA: 4 cases, RAEB in T: 1 case) were treated with myeloablative immunosuppressive therapy followed by bone marrow transplantation (BMT). Median age was 20-y-o (11-31-y-o). All patients were prepared with cyclophosphamide and total body irradiation. Engraftment was documented in all patients. One patients (case 4, 31-y-o female) died of brain hemorrhage due to the thrombocytopenia refractory to platelet transfusion because of anti-platelet antibody in 34 days after BMT. A patient with RAEB in T was also died of respiratory failure from interstitial pneumonia on Day 173. One patient (case 1, 22-y-o, female) progressively became granulocytopenic and thrombocytopenic status after BMT. She suffered from life-threatening infection and then received a second bone marrow cell infusion from the same donor without any preparative conditioning. These results suggest that BMT could be the treatment of choice for MDS, especially for the patients with RA who have poor prognostic factors including life-threatening cytopenia and or cytogenetical abnormalities.

Adolescent↗
PubMed1990

[Pharmacogenetic studies on analgesic activity of and physical dependence on morphine in BALB/c, C57BL/6 inbred mice and these recombinant CBF1 mice].

Mice of the BALB/c, C57BL/6, and CBF1 strains were studied with respect to analgesic activity of and physical dependence on morphine. The acute administration of morphine resulted in analgesic response in the three strains with the following ranking orders: BALB/c greater than C57BL/6 = CBF1 for 5 mg/kg, and C57BL/6 greater than BALB/c greater than CBF1 for 10 and 20 mg/kg. Mice were treated with morphine-admixed food (1-3 mg/g of food) for 9 days. During the treatment, morphine intake in BALB/c was lower than those in C57BL/6 and CBF1. Thus, we examined the degree of physical dependence in three mouse strains after chronic morphine injections for 10 days. There was significant difference in naloxone-precipitated body weight loss among strains, the ranking being as follows: BALB/c greater than CBF1 greater than C57BL/6. However, there was no difference in appearance rate of naloxone-precipitated jumping, but a difference in body shakes and body weight loss, among strains. These results suggest that analgesia of and preference for morphine, and naloxone-precipitated weight loss and body shakes may be influenced by genetic factors.

Administration, Oral↗
PubMed1990

[The effect of diazepam on exploratory behavior and its strain differences in inbred rats].

The effect of diazepam on exploratory behavior was investigated in two inbred strains of rats, Fischer 344 (F344) and Lewis (LEW). The total numbers of head-dips and head-dipping duration in the rat hole-board test, and the total number of rearing and locomotor activity in the open-field test were measured after diazepam administration. The numbers of head-dips and rearings, and head-dipping duration and locomotor activity in naive F344 were significantly greater than those in naive LEW (P less than 0.001), suggesting that LEW is more emotional than F344. Diazepam, 0.31 and 0.63 mg/kg for F344 and 0.31-1.25 mg/kg for LEW, increased head-dips, head-dipping duration and rearings. However, there were no strain differences in enhancing effect of diazepam on locomotor activity. On the contrary, higher doses of diazepam, 0.94-2.50 mg/kg for F344 and 2.50 mg/kg for LEW, decreased head-dips, head-dipping duration, and rearings. However, the effect of diazepam on rotarod performance in LEW was similar to that in F344. These results suggest that F344 is more sensitive to sedative effect of diazepam than LEW, and that the sensitivity to diazepam may be strongly influenced by genetic factors.

Animals↗
PubMed1989

[Effects of flutropium bromide, a new antiasthma drug, with repeated administration on bronchomotor response and hepatic drug metabolizing enzymes].

Effects of flutropium bromide, a new antiasthma drug possessing the quarternary ammonium structure of atropine derivatives, were investigated on the bronchodilatory activity with repeated inhalations in guinea pigs and on the hepatic drug metabolizing enzyme activities with repeated i.v. administration in rats. Single inhalation of flutropium bromide (0.03%) inhibited the ACh-induced bronchoconstriction without changing the fall in blood pressure induced by ACh. Flutropium bromide (0.03%) was inhaled for 5 min a day by placing the animal in an inhalation box, successively during periods of 14 and 28 days. The bronchodilatory effect of flutropium bromide after 14- or 28-day repeated inhalations was almost the same potency as that after single inhalation. Twenty-eight-day repeated inhalations did not change the body weight curve in guinea pigs; and in addition, 14-day repeated i.v. administration did not change the hepatic drug metabolizing enzyme activities in rats. From the above results, it is indicated that flutropium bromide causes neither reduction in response nor cumulative effect after repeated inhalations, and that the agent maintains the bronchodilatory effect without change in the hepatic drug metabolizing enzyme activities.

Acetylcholine↗
PubMed1989

[Effects of inhaled bromhexine on the bronchomotor tone in rats and guinea pigs].

Bromhexine has been widely used as a mucolytic expectorant. Clinically, bromhexine is sometimes administered by inhalation. However, the effect of bromhexine by inhalation on bronchial musculature has not been documented. In the present study, the effect of inhaled bromhexine on bronchomotor tone in rats and guinea pigs was investigated. The bronchomotor tone was measured by a modified Konzett-Rössler method, and ventilation overflow (VO) was continuously recorded as an index of airway resistance. In rats, inhalation of bromhexine (0.1% and 0.2%, pH 5.3) caused no change in VO. At 0.2%, bromhexine slightly decreased systemic blood pressure (BP). In guinea pigs, bromhexine had no significant effect on VO at 0.2%, and it produced a significant but very slight increase at 0.1%. BP was slightly decreased by inhalation of bromhexine (0.1% and 0.2%, pH 5.3). N-Acetyl-L-cysteine, a cysteine-mucolytic (20%, pH 6.8), had no effect on VO and BP in either species. Inhalation of 0.1% bromhexine solution at pH 2.5, which was dissolved in tartaric acid solution, significantly increased VO, because of its acidity. From the above results, it is suggested that when the pH of the solution is considered, bromhexine has no or almost negligible effect on airway smooth muscles, and it may be useful as an effective mucolytic.

Administration, Inhalation↗
PubMed1989

A new bronchial asthma model using calcium ionophore A23187 in guinea pigs.

We attempted to develop a nonimmunologically induced asthma model using the calcium ionophore A23187. Inhalation of A23187 (0.001-0.005%) for 5 min in male Hartley guinea pigs caused a marked bronchoconstriction in a dose-dependent manner with negligible effect on systemic blood pressure. The A23187-induced bronchoconstriction was strongly inhibited by chlorpheniramine and FPL-55712. These results indicate that an asthma-like bronchoconstriction was induced by inhalation of A23187 in guinea pigs, and the main chemical mediators involved in this response would be histamine and peptidoleukotrienes.

Administration, Inhalation↗
PubMed1989

[Relationships between ethanol-induced sleep and aspirin, indomethacin or PGE2 in inbred rats].

It is known that prostaglandin synthetase inhibitors (PGSI) inhibit ethanol (EtOH)-induced sleep in mice, and that EtOH increases production of prostaglandins (PGs). EtOH hypnosis and effects of prostaglandins on EtOH-induced sleeping in inbred rats were examined. The EtOH (3 g/kg, i.p.)-induced sleep time was significantly longer in Fischer 344 (F344) than in Lewis (LEW); blood EtOH concentrations (BAC) on awaking were significantly lower in F344 than in LEW. When aspirin (ASP) and indomethacin (IND) were given 15 and 30 min prior to EtOH administration, respectively, both strains significantly slept shorter than those receiving no PGSI. The BACs on awaking in both strains receiving PGSI were higher than those receiving no PGSI. When LEW and F344 rats were pretreated with PGE2 (0.05-0.5mg/kg, s.c.) 30 min prior to EtOH administration, either strain slept significantly shorter as compared with those receiving EtOH alone. The BACs on awaking were significantly higher in the animals receiving the combination of PGE2 and EtOH than those receiving EtOH alone. These results suggest that there is the strain difference between F344 and LEW in ethanol-induced sleep, and that PGs may, in part, play a role in EtOH-induced sleep in LEW and F344.

Animals↗
PubMed1989

[Ethanol-induced discriminative stimulus properties in inbred rats with reference to aspirin, indomethacin and desipramine].

It is known that ethanol (EtOH) possesses discriminative stimulus (DS) effects, but there has been no report on the effects of aspirin, indomethacin and desipramine on the DS properties of EtOH. Lewis (LEW) and Fischer 344 (F344) rats weighing approximately 80% of free-fed animals were used. In the training process, EtOH (600 and 1200 mg/kg) or saline was administered i.p. once a day 5 min prior to beginning of the session according to the following sequence: EtOH-EtOH-saline-saline, under a fixed ratio ten (FR10) schedule. Discriminative test was performed in each animal after the discriminative response had achieved both the two criteria: (1) First Food Pellet (FFP) was below 12 responses and (2) the correct response rate was above 80%. There was no difference in session number to get to the criteria in the discrimination process between LEW and F344. Pentobarbital (PBA) well generalized to EtOH in both strains. The EtOH dose for 50% correct responses (FD50) was lower in F344 than in LEW. However, the ED50 for PBA was lower in LEW than in F344. There may be differences in sensitivity to EtOH and PBA. Dose response curve was not affected by pretreatment with aspirin, indomethacin and desipramine. These results suggest that aspirin, indomethacin and desipramine may not markedly affect in EtOH discriminative stimulus effects in LEW and F344 rats.

Animals↗
PubMed1988

Sex differences in physical dependence on methaqualone in the rat.

The establishment of, and sex differences in, physical dependence on methaqualone (MQ) in rats were studied by the drug-admixed food (DAF) method. Female and male rats were treated with MQ-admixed food on the same schedule of gradually increasing doses (0.5 and 1 to 6 mg of methaqualone/g of food). Only female rats showed hypothermia from MQ at 1 and 2 mg/g and motor incoordination from MQ at 4 and 6 mg/g of food. Moreover, after MQ withdrawal, severe withdrawal signs, including convulsions and death, were observed in female rats, but not in male rats. We also instituted a different schedule of graded increases in dose (1 and 2 to 10 and 12 mg/g of food) to develop physical dependence on MQ in male rats. Under this schedule male rats exhibited a hypothermia and severe motor incoordination from MQ 6 and 8 mg/g of food condition. After MQ withdrawal, various severe signs of MQ withdrawal occurred, including tremor, convulsions and death. These results demonstrate that severe physical dependence on MQ in both sexes can be established using the DAF method, and that there are marked sex differences in the physical dependence on MQ.

Animals↗