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Biomedical subjects

M Misawa

Publications and source records attributed to M Misawa.

At least 199 records · Page 11Linked to original sources
PubMed1991

Pertussis toxin abolishes mu- and delta-opioid agonist-induced place preference.

The effects of i.c.v. treatment with pertussis toxin (PTX) on the motivational effect of opioid agonists were examined in mice. Morphine (0.1-10 nmol, i.c.v.), [D-Ala2, N-MePhe4, Gly-ol5]enkephalin (DAGO, 0.001-0.1 nmol, i.c.v.), a selective mu-opioid receptor agonist, and [D-Pen2, D-Pen5]enkephalin (DPDPE, 1-15 nmol, i.c.v.), a selective delta-opioid receptor agonist, produced a dose-related place preference in mice. Administration of PTX (0.5 micrograms, i.c.v.) to mice resulted in no preference for either the drug- or vehicle-associated place. Pretreatment with PTX abolished the place preferences induced by DAGO (0.1 nmol), morphine (10 nmol) and DPDPE (15 nmol). These findings demonstrate that the appetitive effects of opioids result from the activation of central mu- and delta-receptors, and suggest that PTX-sensitive GTP-binding proteins in the central nervous system may be involved in the motivational effects of mu- and delta-opioid agonists.

Animals↗
PubMed1991

Potentiation of pentazocine conditioned place preference by tripelennamine in rats.

The effects of tripelennamine on place preference conditioning in rats with pentazocine were investigated. Pentazocine at a dose of 2 mg/kg (IP) slightly, but not significantly, induced a place preference. Concurrent dosing of pentazocine (2 mg/kg, IP) and tripelennamine (2.5 mg/kg, SC) significantly and prominently produced a place preference, although administration of tripelennamine (2.5 mg/kg, SC) alone did not. Chronic infusion of a dopamine D1 receptor antagonist, SCH23390 (1.0 mg/kg/day) during conditioning abolished the appetitive effect of pentazocine potentiated by the combination with tripelennamine. In conclusion, it is suggested that the dopaminergic system, especially at the D1 receptor, plays an important role in the potentiation effect of tripelennamine on the pentazocine-induced place preference.

Animals↗
PubMed1991

Pentazocine-induced biphasic analgesia in mice.

Pentazocine (PZ) is well known to act as an opioid mixed agonist-antagonist analgesic. In the present study, we selected the mouse warm plate test condition of 51 +/- 0.5 degrees C instead of 55 +/- 0.5 degrees C to determine the analgesic action of PZ. As a result, i.c.v. PZ produced a biphasic antinociceptive response, while U-50,488H (U-50) and morphine (MRP) showed a monophasic response. Pretreatment with i.c.v. beta-FNA (mu antagonist) antagonized the initial response, whereas the delayed one was antagonized by pretreatment with nor-BNI (kappa antagonist). In addition, pretreatment with NTI (delta antagonist) significantly attenuated the initial response but not the delayed one. These results suggest that the initial and delayed responses may be mediated mainly by mu/delta and kappa receptors, respectively. With regards to the interaction between MRP and PZ, a low dose of PZ antagonized the analgesic action of MRP, while a high dose PZ plus MRP showed the additive effect. Furthermore, tolerance developed almost equally to both initial and delayed responses, indicating that tolerance to the kappa component of PZ may be developed as well as the mu component of action of PZ.

3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cycloh↗
PubMed1991

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

The effect of platelet-activating factor (PAF) on histamine release from the peritoneal mast cells of male guinea pigs at 4 weeks of age and one week of age (weaning) was investigated. PAF as well as compound 48/80 and concanavalin A were not found to release histamine from the mast cells of either age of guinea pigs. On the other hand, Ca2+ ionophore A23187 showed a significant, concentration-dependent histamine release from the mast cells obtained from guinea pig of either age group. PAF (3 x 10(-7) - 3 x 10(-6) g/ml) significantly inhibited the histamine release induced by Ca2+ ionophore A23187 from the mast cells of guinea pigs at one week of age, but not from those of the older ones. Such an inhibition was not seen with lyso-PAF in either age group. CV-3988, a PAF antagonist, neutralized the inhibitory effect of PAF on the A23187-induced histamine release from the mast cells of guinea pigs at one week of age. These results indicate that PAF does not have a histamine-liberating action on guinea pig peritoneal mast cells, and that PAF inhibits the effect of A23187 on histamine release from mast cells through activation of PAF receptor in guinea pigs at one week of age.

Animals↗
PubMed1991

Differential sensitivity to physical dependence on morphine and codeine in three inbred strains of mice.

The purpose of this experiment is to investigate genetic differences in the development of physical dependence on morphine and codeine in inbred strains of mice, C57BL/6, C3H/He and DBA/2. Mice were treated with morphine- or codeine-admixed food (1, 2 and 3 mg/g of food) for 3 to 9 days. After the termination of drug treatment, the mice were given naloxone (5 mg/kg, s.c.). The incidences of jumping and teeth chattering by naloxone challenge in morphine- and codeine-treated C57BL/6 mice were much greater than those in C3H/He and DBA/2 mice. However, the incidences of other naloxone-precipitated withdrawal signs, such as ptosis and diarrhea, were not different among the three inbred strains of mice. These results indicate that genotype is an important determinant of the degree of most naloxone-precipitated withdrawal signs in morphine- and codeine-treated mice.

Animals↗
PubMed1991

[Dr. Hideyo Noguchi and Hajime Hoshi].

Hajime Hoshi is a founder of Hoshi Pharmaceutical Company and of Hoshi University. He became acquainted with Dr. Hideyo Noguchi in the United States in 1901 during his study abroad. Hoshi often stayed overnight at Noguchi's apartment in Philadelphia. Hoshi and Noguchi were both from Fukushima, Japan, and Hoshi was three years older than Noguchi. Both persons had been good friends until Hoguchi died in 1928. Hoshi and Noguchi together had met Hirobumo Ito and Thomas Edison. In 1906, Hoshi came back to Japan after a 12-year stay in the United States. The financial support by Hoshi enabled the only and one temporary returning of Noguchi to Japan in 1915. In this paper, the friendship between the famous two persons is described in detail.

History of Pharmacy↗
PubMed1991

Effects of the new antiallergic drug epinastine and ketotifen on repeated antigen challenge-induced airway hyperresponsiveness in rats.

Airway hyperresponsiveness (AHR) is a critical component in bronchial asthma, probably associated with airway inflammation. The effects of epinastine (WAL-801 CL, CAS 80012-43-7), a new antiallergic drug, and ketotifen on AHR were investigated with a new AHR model in rats. Male Wistar rats which were actively sensitized with DNP-Ascaris (DNP-Asc) antigen, were challenged by inhaling DNP-Asc 3 times every 48 h. The airway responsiveness to inhaled ACh was determined 24 h after the last antigen challenge by modified Konzett-Rössler method under anesthesia with urethane. Antiallergic drugs were given orally 1 h before each antigen challenge in case of single treatment, and 3 times a day for 5 days in case of chronic treatment. The airway responsiveness to inhaled ACh was significantly increased after the repeated antigen challenge. Single treatments with epinastine and ketotifen did not inhibit AHR induced by repeated antigen challenge. On the other hand, chronic epinastine and ketotifen treatments, significantly inhibited the enhancement of AHR. From the above results, it is suggested that chronic treatments with epinastine and ketotifen are effective even for therapy of AHR.

Acetylcholine↗
PubMed1991

Developmental changes in serotonergic neurons by maternal ethanol consumption in the rat offspring.

The brain levels of 5-hydroxytryptamine (5-HT) and 5-hydroxyindoleacetic acid (5-HIAA), the synthesis rate of 5-HT and 5-HIAA, and the elimination rate of 5-HIAA in the rat offspring brain exposed to ethanol were examined. Ethanol was administered as a drinking water (group L) and in combination with 4 g/kg. p.o. of ethanol (group H) to the pregnant mothers during days 3 to 21 of gestation. There was no difference in brain 5-HT levels between control and groups L and H at 2, 3, 4 and 6-7 weeks of age. A significant decrease in brain 5-HIAA levels was observed at 3 and 6-7 weeks of age in group L and group H, respectively. In the pups of group H, the 5-HT synthesis rate and the elimination rate of 5-HIAA reduced at 4 and 6-7 weeks of age in comparison with the respective control pups. On the other hand, in the pups of group L, the 5-HT synthesis rate increased, and the 5-HIAA synthesis rate reduced at 3, 4 and 6-7 weeks of age. These results suggest that differential exposure to ethanol, such as group L and H, in the CNS during developmental period induces a differential change in the activity of serotonergic system.

Age Factors↗
PubMed1991

Effect of the new antiallergic drug epinastine on chemical mediator induced bronchoconstrictions in guinea pigs.

Recently, mast cell stabilizers, so called antiallergic drugs, that also have blocking effects on receptors for chemical mediators (CM) have been developed. The present study investigated the effects of a new antiallergic drug, epinastine (3-amino-9,13b-dihydro-1H-dibenz[c,f]imidazol [1,5-a]azepine hydrochloride, WAL 810 CL; CAS 80012-43-7) on the in vivo bronchoconstriction (BC) induced by several CM as compared with those of other antiallergic drugs such as ketotifen, azelastine and oxatomide. Male Hartley guinea pigs were used. The BC was measured with a modified Konzett-Rössler method and expressed as a change in ventilation overflow (VO) under anesthesia. Antiallergic drugs were given orally 1 h before i.v. administration of CM. I.v. administrations of histamine (His), U-46619 (thromboxane A2 mimetic), leukotriene D4 (LTD4), prostaglandin D2 (PGD2), substance P (SP), neurokinin A (NKA), bradykinin (BK) and endothelin-1 (ET-1) increased VO in a dose dependent manner. The potency was as follows; ET-1 greater than LTD4 greater than NKA much greater than U-46619 greater than SP greater than His greater than BK much greater than PGD2. All the antiallergic drugs used markedly inhibited the His-induced BC. Epinastine, ketotifen and azelastine also significantly inhibited the BK-induced BC; epinastine had the strongest anti-BK effect among them. On the other hand, the four antiallergic drugs did not inhibit the BC induced by the other CM except for His and BK. Based on the above results, it is suggested that epinastine possesses anti-His and BK effects, and therefore could be promising as a new antiallergic drug without sedative effect.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗
PubMed1991

Biochemical and immunohistochemical analysis of orotic acid-induced fatty liver.

Orotic acid-induced fatty livers were examined by biochemical and immunohistochemical approaches. Lipid peroxide levels by the thiobarbituric acid method and glutathione-peroxidase (GSH-PO) activity in the liver homogenates from orotic administered rats were similar to those of controls. Immunohistochemical localization of GSH-PO in orotic acid-induced fatty liver was mainly observed in the portal zone of the hepatic lobules. This staining pattern of GSH-PO was similar to that of the controls. No remarkable changes in GSH-PO staining patterns were detected in orotic acid-induced fatty liver. Our data strongly suggested that no lipid peroxidation is actively involved in the genesis of fatty liver due to the administration of orotic acid, and GSH-PO a protective enzyme against lipid peroxidation, was not inhibited by orotic acid-induced fatty liver.

Animals↗
PubMed1990

Enhancement of morphine withdrawal signs in the rat after chronic treatment with naloxone.

Chronic treatment of rats with naloxone for 5 days increased the analgesic threshold (hot plate latency). Further, when rats were treated with morphine-admixed food for 3 days after the chronic naloxone treatment the withdrawal signs precipitated by naloxone were significantly greater in the naloxone-pretreated rats than in saline-pretreated rats. These results suggest that paradoxical analgesia and enhancement of the morphine withdrawal signs induced by chronic naloxone treatment may be associated mainly with up-regulation of mu- and delta-opioid binding sites in the central nervous system.

Analgesia↗
PubMed1990

Human G-CSF produced by adherent cells in the presence of human recombinant GM-CSF.

Adherent cells (AdCs) in blood from normal volunteers produced granulocyte-macrophage (GM) colony-stimulating activity (CSA) in the presence of 10 ng/ml of recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF) in vitro. GM-CSA produced by adherent cells in the presence of GM-CSF reached a plateau level on day 6. Colonies stimulated by adherent cell-conditioned medium (AdC-CM-GM-CSF), which had been harvested after 6 days of incubation of AdCs with rhGM-CSF, were granulocyte predominant. When phagocyte-depleted marrow mononuclear cells (PD-M-MNCs) were cultured with AdC-CM-GM-CSF and anti-rabbit serum against rhGM-CSF, 99% of the colonies on day 7 were exclusively composed of neutrophils. When 2 X 10(4) PD-M-MNCs were cultured in a medium containing AdC-CM-GM-CSF, AdC-CM-GM-CSF + anti-GM-CSF, AdC-CM-GM-CSF + anti-G-CSF, or AdC-CM-GM-CSF + both of the anti-bodies, the PD-M-MNCs formed (mean +/- SD) 100 +/- 2.0%, 64.3 +/- 2.5%, 38.6 +/- 0.4%, and 6.0 +/- 0.4% GM colonies, respectively. Furthermore, northern blot analysis revealed that AdCs incubated with 10 ng/ml of rhGM-CSF for 6 h expressed much more mRNA of G-CSF than those without the CSF. These data indicated that AdCs in blood produce G-CSF in the presence of GM-CSF.

Blotting, Northern↗
PubMed1990

Drug interactions in the reinforcing effects of over-the-counter cough syrups.

Drug interactions in reinforcin effects of over-the-counter cough syrups were investigated by utilizing place preference conditioning in rats. Dihydrocodeine (2 mg/kg, IP) induced a small, non-significant place preference. On the other hand, concurrent dosing of dihydrocodeine (2 mg/kg, IP) and a mixture (SC) of methylephedrine (4 mg/kg), caffeine (4 mg/kg) and chlorpheniramine (0.8 mg/kg) produced a significant place preference, the mean conditioning score in this group being about 3 times higher than that in the dihydrocodeine alone group. The potentiation of dihydrocodeine-conditioned place preference was observed by combination with chlorpheniramine (0.8 mg/kg, SC) alone as well as with the mixture, but neither with methylephedrine (4 mg/kg, SC) nor with caffeine (4 mg/kg, SC). Chronic infusion of the dopamine D1 receptor antagonist SCH23390 (1.0 mg/kg/day, SC) during conditioning abolished the appetitive effects of dihydrocodeine combined with chlorpheniramine. In conclusion, it is suggested that the potentiation of appetitive effects of dihydrocodeine is mostly due to chlorpheniramine among three ingredients in the cough syrups, and that the dopaminergic system, especially D1 receptor, may play an important role in the potentiation effect of chlorpheniramine on the reinforcing effects of dihydrocodeine.

Animals↗
PubMed1990

"Paradoxical" analgesia and aggravated morphine dependence induced by opioid antagonists.

Chronic treatment with naloxone (Nx) or naltrexone (Ntx) induces paradoxical analgesia. In the present study, the effects of chronic treatment with opioid receptor antagonists, such as nor-binaltorphimine (nor-BNI) for kappa and naltrindole (NTI) for delta receptors, on analgesic response using the hot plate test and on morphine physical dependence in rats were examined. The hot plate latency was significantly increased by pretreatment with Nx (5 mg/kg, s.c.), nor-BNI (20 mg/kg, i.p.) or NTI (20 mg/kg, i.p.) for 5 days. After chronic pretreatment with these antagonists, the rats were treated with morphine-admixed food (0.5 mg/g of food) for 3 days. Chronic pretreatment with Nx and NTI significantly increased Nx precipitated body weight loss in morphine dependent rats, while chronic pretreatment with nor-BNI produced small increase. These results indicate that chronic treatment with nor-BNI or NTI as well as with Nx induces obviously paradoxical analgesia, and that chronic blockade of mu or delta may enhance the development of physical dependence on morphine.

Animals↗
PubMed1990

Immunohistochemical demonstration of nonspecific cross-reacting antigen in normal and neoplastic human tissues using a monoclonal antibody. Comparison with carcinoembryonic antigen localization.

Nonspecific cross-reacting antigen (NCA) immunoreactivity was localized in normal and neoplastic human tissues using a monoclonal antibody to 55, 90 and 95 kDa molecules of NCA. This was compared to the localization of immunoreactive carcinoembryonic antigen (CEA) as demonstrated by polyclonal and monoclonal antibodies. In frozen sections, CEA was localized in normal surface epithelium of the stomach and colon where NCA was only weakly detected. Type 1 and type 2-like pneumocytes were positive for NCA, while CEA was localized only in type 2-like pneumocytes. CEA and NCA were both demonstrated in ductal cells of frozen pancreatobiliary and mammary tissues. The antigenicity of CEA and NCA in normal tissues was significantly lost after paraffin embedding as compared to frozen sections. NCA was consistently demonstrated in eccrine sweat glands embedded in paraffin. In various tumor tissues, CEA and NCA were colocalized and expression increased sufficiently to be detected in paraffin sections. Adenocarcinomas of the stomach and colon and cystadenocarcinoma of the pancreas, as well as neuroendocrine carcinomas of the lung and thyroid, showed a CEA predominance over NCA. In ductal adenocarcinomas of the pancreas and breast and in cholangiocarcinoma, NCA reactivity was greater than CEA. Keratinizing foci of most squamous cell carcinomas of mucosal origin and some adenocarcinomas equally expressed both. Hepatocellular carcinoma, lobular mammary carcinoma and papillary thyroid carcinoma were positive only with unabsorbed polyclonal antibody which widely recognizes CEA-related substances. Renal cell carcinoma, prostatic adenocarcinoma, transitional cell carcinoma, anaplastic carcinomas, choriocarcinoma and basal cell carcinomas showed little or no immunoreactivity. Hence the relative ratio of CEA/NCA expression in tumors was dependent on the tissue of origin and histologic type. The cytoplasmic granular staining of NCA in cancer cells was a noteworthy difference from the plasma membrane-associated localization of CEA.

Antibodies, Monoclonal↗
PubMed1990

[Effects of flutropium bromide, a new anti-asthma drug, alone or in combination with salbutamol, aminophylline and disodium cromoglycate on the acetylcholine induced bronchoconstriction].

Effects of flutropium bromide, a new bronchodilator with an anticholinergic action, alone or in combination with other antiasthma drugs were investigated in guinea pigs by using an index of inhibition of the acetylcholine (ACh)-induced bronchoconstriction. Single inhalation of flutropium bromide (0.0003%) into the airways of guinea pigs inhibited the ACh (i.v.)-induced bronchoconstriction without changing the fall in blood pressure induced by ACh. When salbutamol (3 micrograms/kg, i.v.), aminophylline (5 mg/kg, i.v.) or disodium cromoglycate (10 mg/kg, i.v.) was administered in combination with flutropium bromide (0.0003%), bronchodilation was enhanced as compared with single administration of the respective antiasthma drugs. From the above results, it is indicated that inhalation of flutropium bromide provides a more efficient bronchodilation in combination with other antiasthma drugs that possess different mechanisms of antiasthma effects.

Acetylcholine↗
PubMed1990

Involvement of inhibitory innervation in reflex tracheal dilatation induced by lung inflation.

We investigated the involvement of inhibitory innervation in reflex tracheal dilatation (RTD) induced by inflating the lungs in dogs. RTD was inhibited about 50% by 100 micrograms propranolol injected into the cranial thyroid artery, but was unaffected by adrenalectomy. Residual RTD under beta-blockade was abolished by sections of both the bilateral superior laryngeal nerves and spinal cord at the C1 level. These findings suggest that RTD may be mediated by adrenergic innervation and partly by nonadrenergic inhibitory innervation.

Adrenalectomy↗