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Biomedical subjects

A Karasawa

Publications and source records attributed to A Karasawa.

At least 19 recordsLinked to original sources
PubMed2005

Olopatadine hydrochloride suppresses the rebound phenomenon after discontinuation of treatment with a topical steroid in mice with chronic contact hypersensitivity.

BACKGROUND: Olopatadine hydrochloride (olopatadine; Allelock) is one of the second-generation antihistamines that are treated for allergic disorders such as rhinitis, urticaria and eczema dermatitis. Olopatadine has recently been shown to have inhibitory effects on the chronic contact hypersensitivity induced by repeated application of oxazolone in mice. Although topical steroids have widely been prescribed for atopic dermatitis, a relapse often occurs within several days after discontinuation of their prolonged use. OBJECTIVES: We investigated the possible efficacy of olopatadine against the relapse after discontinuation of prolonged use of topical prednisolone in the Balb/c mice with oxazolone-induced chronic contact hypersensitivity. METHODS: Mice with the chronic contact hypersensitivity induced by repeated application of oxazolone were treated with olopatadine as a sequential therapeutic agent. The effects of olopatadine were quantified by measurements of ear-swelling, and levels of cytokines and histamine in the lesioned ear. Results Topical prednisolone (0.05 mg/ear/day) significantly inhibited the increases in ear swelling and production of IL-1beta, IL-4, IL-18, granulocyte-macrophage colony-stimulating factor (GM-CSF) and histamine. However, after discontinuation of the treatment with topical prednisolone, the inflammation relapsed and the IL-4 level exceeded the control one. The sequential treatment with olopatadine (10 mg/kg/day) after discontinuation of the treatment with topical prednisolone alone, or topical prednisolone with olopatadine, significantly inhibited the increases in ear swelling and levels of IL-1beta, IL-4, IL-18, GM-CSF, nerve growth factor and histamine. CONCLUSIONS: These results indicate that olopatadine is an antihistamine agent having inhibitory activities against the rebound phenomenon following the discontinuation of topical steroid therapy. Olopatadine is thus expected to be a sequential therapeutic agent after discontinuation of the chronic treatment with a topical steroid.

Animals↗
PubMed2004

Effects of olopatadine hydrochloride, an antihistamine drug, on skin inflammation induced by repeated topical application of oxazolone in mice.

BACKGROUND: Olopatadine hydrochloride (olopatadine) is one of the second-generation antihistamines, which is prescribed for allergic disorders such as rhinitis, urticaria and eczema dermatitis. OBJECTIVES: To investigate the possible anti-inflammatory effect of olopatadine on the chronic contact hypersensitivity response to repeated topical application of oxazolone in mice. METHODS: The preventive and therapeutic effects of oral olopatadine were quantified by measurements of ear swelling, cytokine protein and mRNA expression in the ear lesion, and were compared with those of topical betamethasone 17-valerate (betamethasone). RESULTS: The ear receiving repeated applications of oxazolone exhibited erythema, oedema and abrasion. Both preventive and therapeutic administration of olopatadine (10 mg kg(-1) day(-1)) significantly inhibited the ear swelling and the increased production of interleukin (IL)-4, IL-1beta, granulocyte-macrophage colony-stimulating factor (GM-CSF) and nerve growth factor. In the histopathological analysis, olopatadine ameliorated epidermal hyperplasia and infiltration of inflammatory cells. Consistent with these results, olopatadine significantly reduced the increased expression of interferon-gamma and IL-4 mRNA. Although betamethasone (0.012 mg ear(-1) day(-1)) showed similar activities to olopatadine against these responses, it caused atrophy of the ear skin. CONCLUSIONS: These results indicate that olopatadine is an antihistamine agent having inhibitory activities against chronic inflammatory dermatitis, possibly resulting from its diminishing effect on elevated cytokines.

Adjuvants, Immunologic↗
PubMed2001

Evaluation of [4-O-methyl-(11)C]KW-6002 as a potential PET ligand for mapping central adenosine A(2A) receptors in rats.

KW-6002, a xanthine-based adenosine A(2A) antagonist, was labelled with the positron emitter carbon-11 by O-methylation of its precursor, KF23325, using [(11)C]iodomethane and was evaluated in rats as a putative in vivo radioligand for positron emission tomography (PET). Following intravenous injection of [(11)C]KW-6002, radioactivity was measured in blood, plasma, peripheral tissues, and in discrete brain tissues over a 2-h time period commensurate with PET scanning. In brain, [(11)C]KW-6002 showed highest retention in striata, with evidence of saturable binding, and lowest retention in frontal cortex (a tissue low in adenosine A(2A) receptors). PET scanning with [(11)C]KW-6002 demonstrated a specific signal in the striata which could be described using compartmental modelling. Specific binding was, however, also detected in extrastriatal regions, including brain areas reported to have low adenosine A(2A) receptor density. Blocking studies with the A(1) selective antagonist KF15372 and the non xanthine-type A(2A) antagonist ZM 241385 failed to elucidate the nature of this binding. Thus, although [(11)C]KW-6002 shows some potential for development as a PET ligand for quantifying striatal adenosine A(2A) receptor function, its in vivo selectivity requires further investigation.

Animals↗
PubMed2001

Roles of mast cells and sensory nerves in cutaneous vascular hyperpermeability and scratching behavior induced by poly-L-arginine in rats.

We investigated whether the polycation poly-L-arginine elicited cutaneous vascular hyperpermeability and scratching behavior and, if so, whether these responses involved mast cells and sensory nerves in rats. Intradermal injections of poly-L-arginine induced vascular hyperpermeability and scratching behavior. Combined treatment with chlorpheniramine and methysergide almost completely suppressed the poly-L-arginine (50 microg/site)-induced plasma leakage. Capsaicin desensitization and the tachykinin NK(1) receptor antagonist LY303870, (R)-1-[N-(2-methoxybenzyl)acetylamino]-3-(1H-indol-3-yl)-2-[N-(2-(4-(piperidin-1-yl)piperidin-1-yl)acetyl)amino]propane, partially inhibited the leakage. In mast cell-deficient rats, poly-L-arginine only minimally induced plasma leakage. On the other hand, capsaicin desensitization and LY303870, but not chlorpheniramine or methysergide, suppressed the poly-L-arginine (200 microg/site)-induced scratching. Moreover, poly-L-arginine elicited the scratching even in mast cell-deficient rats. These results suggest that substance P is at least partly involved in both the cutaneous plasma leakage and the scratching behavior induced by poly-L-arginine. Moreover, mast cell-derived amines are suggested to be involved in the plasma extravasation but scarcely, if any, in the scratching behavior.

Animals↗
PubMed2001

Anti-apoptotic effect of benidipine, a long-lasting vasodilating calcium antagonist, in ischaemic/reperfused myocardial cells.

1. Ischaemia/reperfusion causes intracellular calcium overloading in cardiac cells. Administration of calcium antagonists reduces myocardial infarct size. Recent in vitro studies have demonstrated that calcium plays a critical role in the signal transduction pathway leading to apoptosis. However, whether or not calcium antagonists may reduce myocardial apoptosis induced by ischaemia-reperfusion, and thus decrease myocardial infarction, has not been directly investigated. 2. The present study investigated the effects of benidipine, an L-type calcium channel blocker, on myocardial infarct size, apoptosis, necrosis and cardiac functional recovery in rabbits subjected to myocardial ischaemia/reperfusion (MI/R, 45 min/240 min). Ten minutes prior to coronary occlusion, rabbits were treated with vehicle or benidipine (10 microg x kg(-1) or 3 microg x kg(-1), i.v.). 3. In the vehicle-treated group, MI/R caused cardiomyocyte apoptosis as evidenced by DNA ladder formation and TUNEL positive nuclear staining (12.2+/-1.1%). Treatment with 10 microg x kg(-1) benidipine lowered blood pressure, decreased myocardial apoptosis (6.2+/-0.8%, P<0.01 vs vehicle) and necrosis, reduced infarct size (20+/-2.3% vs 49+/-2.6%, P<0.01), and improved cardiac functional recovery after reperfusion. Administering benidipine at 3 microg x kg(-1), a dose at which no haemodynamic effect was observed, also exerted significant anti-apoptosis effects, which were not significantly different from those observed with higher dose benidipine treatment. However, treatment with this low dose benidipine failed to reduce myocardial necrosis. 4. These results demonstrate that benidipine, a calcium antagonist, exerts significant anti-apoptosis effects, which are independent of haemodynamic changes. Administration of benidipine at a higher dose produced favourable haemodynamic effects and provided additional protection against myocardial necrotic injury and further improved cardiac functional recovery.

Animals↗
PubMed2001

Effects of olopatadine hydrochloride on the increase of histamine and peptide-leukotrienes concentrations in nasal lavage fluid following the antigen-antibody reaction in actively sensitized guinea pigs.

To investigate the mechanism for the amelioration by olopatadine hydrochloride (olopatadine) of allergic rhinitis, we determined its effects on the increase of chemical mediator concentrations in nasal lavage fluid following the intranasal antigen challenge in guinea pigs actively sensitized with DNP-Ascaris. The concentrations of histamine and peptide-leukotrienes increased 10 min after the challenge. Olopatadine at 10 mg/kg (p.o.) significantly prevented the increase of histamine and tended to inhibit the increase of peptide-leukotrienes. The inhibition by olopatadine of the nasal symptoms seems to involve the inhibitory effect on the releases of histamine and, possibly, p-LTs into the nasal cavity.

Animals↗
PubMed2001

Possible involvement of 5-HT4 receptors, in addition to 5-HT3 receptors, in the emesis induced by high-dose cisplatin in Suncus murinus.

To clarify the mechanism for the severe emesis concomitant with intensive chemotherapy, we investigated the effects of 5-HT3- and 5-HT4-receptor antagonists on the emesis induced by the high-dose of cisplatin in Suncus murinus. The emesis induced by 50 mg/kg of cisplatin was reduced by the oral pretreatment with tropisetron, which is known as a 5-HT3- and 5-HT4-receptor dual antagonist in vitro, with the ID50 value of 0.52 mg/kg. On the contrary, granisetron, a selective 5-HT3-receptor antagonist, did not markedly inhibit the emesis at up to 30 mg/kg. Moreover, GR125487, a selective 5-HT4-receptor antagonist, did not inhibit the emesis. However, co-administration of GR125487 and granisetron significantly reduced the number of emetic episodes. The study of the co-administration of GR125487 with tropisetron showed that GR125487 did not further enhance the inhibitory effect of tropisetron alone, suggesting that the anti-emetic effect of tropisetron is mediated via the blockade of both 5-HT3 and 5-HT4 receptors. These results suggest that both the 5-HT3 and 5-HT4 receptors are involved in the emesis induced by the high-dose of cisplatin in Suncus murinus.

Animals↗
PubMed2001

Involvement of neuropeptides in the allergic nasal obstruction in guinea pigs.

The purposes of the present study were i) to determine whether neuropeptides induce the nasal obstruction in guinea pigs, and ii) to examine the possible involvement of neuropeptides in allergic nasal obstruction. The decrease in nasal cavity volume was determined by acoustic rhinometry as an index of nasal obstruction. In non-sensitized guinea pigs, substance P (SP), neurokinin A (NKA) and calcitonin gene-related peptide (CGRP) caused the nasal obstruction 10 to 30 min after their intranasal application. LY303870 (1 mg/kg), a tachykinin NK1-receptor antagonist; SR48968 (1 mg/kg), a tackykinin NK2-receptor antagonist; and CGRP(8-37) (50 nmol/kg), a CGRP1-receptor antagonist, administered intravenously before the intranasal application of the neuropeptides, inhibited the responses induced by SP, NKA and CGRP, respectively. In the guinea pigs sensitized with dinitrophenyl-coupled Ascaris suum allergenic extract, the intranasal antigen challenge caused nasal obstruction. The response was biphasic and consisted of the early phase response (EPR) and the late phase response (LPR), which developed 30 min and 6 h, respectively, after the antigen challenge. Intravenous administration of LY303870 (1 mg/kg) before the antigen challenge inhibited the EPR, while those of SR48968 (1 mg/kg) and CGRP(8-37) (50 nmol/kg) inhibited the LPR. The present results suggest that neuropeptides are involved in the allergic nasal obstruction.

Animals↗
PubMed2001

Inhibitory effect of olopatadine hydrochloride on the sneezing response induced by intranasal capsaicin challenge in guinea pigs.

To investigate the possible inhibitory effect of olopatadine hydrochloride (olopatadine), an antiallergic drug, on the tachykinin-mediated nasal responses, we examined the effect of olopatadine on the sneezing and the nasal rubbing responses induced by intranasal capsaicin challenge in guinea pigs. Olopatadine (10 mg/kg, p.o.) inhibited the sneezing response by 57% without affecting the nasal rubbing one. The antihistamines chlorpheniramine and clemastine did not affect the responses. Morphine caused the inhibition of both responses, which was antagonized by naloxone. These results suggest that olopatadine inhibits the sneezing response by the inhibition of the tachykinin release and not by its antihistaminic action.

Administration, Intranasal↗
PubMed2001

Effects of olopatadine hydrochloride on the cutaneous vascular hyperpermeability and the scratching behavior induced by poly-L-arginine in rats.

Intradermal injections of poly-L-arginine induce cutaneous vascular hyperpermeability and scratching behavior in rats. Recently, we elucidated that the plasma extravasation involved both histamine and substance P, while the scratching behavior involved substance P, but not histamine. This study examined the effects of olopatadine hydrochloride (olopatadine), an antiallergic drug with histamine H1-antagonistic action, on the poly-L-arginine-induced responses. Olopatadine (1 mg/kg, p.o.) significantly inhibited both the plasma extravasation and the scratching behavior, suggesting that its inhibitory effects are mediated by the suppression of neuropeptidergic action as well as histaminic action. Olopatadine seems to be a novel-type drug for the treatment of dermatitis.

Animals↗
PubMed2000

Change of the involvement of 5-HT3 receptor in the gastric motor stimulating actions of KW-5139 (Leu13-motilin acetate) in the recovered and post-operative periods in dogs.

We have previously reported that KW-5139, a motilin analogue, evokes gastrointestinal motor stimulating action in the post-operative period as well as in the recovered period of conscious dogs. In this report, we compared the mechanisms of the KW-5139-induced contractions in the post-operative period with those in the recovered period using beagle dogs implanted force transducers in the gastric antrum, duodenum, jejunum, ileum and colon. In addition, we also examined the mechanisms of the prostaglandin F2alpha-induced contractions in both periods. The gastric contractions evoked by KW-5139 (0.5 microg kg(-1), i.v.) were inhibited by the pretreatment of ondansetron (0.1 mg kg(-1), i.v.), a 5-HT3 receptor antagonist, in the recovered period, but were not affected in the post-operative period even by higher doses of ondansetron (0.3-1 mg kg(-1), i.v.). The KW-5139-induced contractions in the small and large intestine were not inhibited by ondansetron in the both periods. The contractions evoked by KW-5139 (0.5 microg kg(-1), i.v.) in the gastric antrum, duodenum, jejunum and colon were significantly inhibited by the pretreatment with atropine (0.05 mg kg(-1), i.v.), a muscarinic receptor antagonist, in the recovered period as same extent as in the post-operative period. The contractions evoked by prostaglandin F2alpha (50 microg kg(-1), i.v.) in the any recording sites were not affected by the pretreatment with ondansetron (0.1 mg kg(-1), i.v.) in the recovered period. On the other hand, atropine (0.05 mg kg(-1), i.v.) tended to inhibit the gastric and colonic contractions. These effects of ondansetron and atropine on the prostaglandin F2alpha-induced contractions were not different between in the post-operative and recovered periods. The present results indicate that 5-HT3 receptors are involved in the KW-5139-induced motor stimulating action in the recovered period but not in the post-operative period. The mechanisms of the alteration were discussed.

Anesthesia Recovery Period↗
PubMed2000

Effect of zaldaride maleate, an antidiarrheal compound, on intracellular cyclic nucleotide-mediated intestinal ion secretion in rats.

The purpose of this study is to clarify the mechanisms of action of zaldaride, a calmodulin inhibitor. 16,16-Dimethyl prostaglandin E(2), forskolin, 8-bromo cAMP, nitroprusside, 8-bromo cGMP and Escherichia coli heat-stable enterotoxin STa increased the short-circuit current in rat colonic mucosa. Zaldaride at >/=10 microM significantly attenuated the 16,16-dimethyl prostaglandin E(2) and Escherichia coli heat-stable enterotoxin STa-induced increase in short-circuit current; whereas it did not affect other secretagogues-induced effects. These results suggest that zaldaride inhibits the activation of Ca(2+)/calmodulin-sensitive adenylate cyclase or guanylate cyclase linked to a receptor.

16,16-Dimethylprostaglandin E2↗
PubMed2000

The effect of zaldaride maleate, an antidiarrheal compound, on acetylcholine-induced intestinal electrolyte secretion.

The effect of zaldaride on acetylcholine-induced colonic electrolyte secretion was examined. The short-circuit current response to acetylcholine was partially reduced by tetrodotoxin, a neuronal blocker, and was completely inhibited by atropine, an acetylcholine M receptor antagonist, in the rat colonic preparations. The tetrodotoxin sensitive effect was significantly inhibited by zaldaride, whereas the tetrodotoxin insensitive effect was not affected. Acetylcholine release from synaptosomes of submucosal nerves of guinea-pig colon was significantly reduced by zaldaride. Zaldaride may reduce colonic electrolyte secretion by acetylcholine due to the inhibition of acetylcholine release from synaptosomes of colonic submucosal nerves.

Acetylcholine↗
PubMed2000

Effect of zaldaride maleate, an antidiarrheal compound, on 16,16-dimethyl prostaglandin E2-induced intestinal ion secretion in rats.

The effect of zaldaride, a calmodulin inhibitor, on 16,16-dimethyl prostaglandin E2 (dmPGE2)-induced intestinal ion secretion was investigated in rats. Zaldaride inhibited the dmPGE2-induced increase in water content in the colon, but not that in the small intestine. In the colonic mucosa, zaldaride attenuated the dmPGE2-induced short-circuit current; however, it did not affect the forskolin or dibutyryl cAMP-induced effect. These results suggest that zaldaride inhibits dmPGE2-induced intestinal ion secretion by reducing the activity of Ca2+/calmodulin-dependent adenylate cyclase linked to a receptor, and the colon may be an important site in the action of zaldaride.

16,16-Dimethylprostaglandin E2↗
PubMed2000

Effects of zaldaride maleate, an antidiarrheal compound, on intracellular Ca2+-mediated short-circuit current response in the rat colonic mucosa.

The effect of zaldaride maleate (ZAL) on intracellular Ca2+-mediated short-circuit current (Isc) response in rat colonic mucosa was investigated. The Isc response to acetylcholine was partially reduced by the neuronal blocker tetrodotoxin. The tetrodotoxin-sensitive Isc response to acetylcholine was inhibited by ZAL. The tetrodotoxin-insensitive effect, which indicates direct stimulation of acetylcholine in colonic mucosa, was not affected by ZAL. The Isc response to the Ca2+ ionophore A23187 was reduced by ZAL in the presence of tetrodotoxin. These results suggest that ZAL reduces colonic ion secretion by inhibiting a tetrodotoxin-sensitive neuronal pathway and an intracellular Ca2+ pathway in epithelium.

Acetylcholine↗
PubMed2000

Effect of the selective adenosine A1-receptor antagonist KW-3902 on lipopolysaccharide-induced reductions in urine volume and renal blood flow in anesthetized dogs.

We investigated the effects of KW-3902 (8-noradamantan-3-yl-1,3-dipropylxanthine), a potent and selective adenosine A1-receptor antagonist, on lipopolysaccharide (LPS)-induced reduction of urine volume (UV) in anesthetized dogs, in comparison with those of furosemide. LPS was intravenously administered at a dose of 0.5 mg/kg; and the heart rate (HR), systemic blood pressure (BP), renal blood flow (RBF) and UV were measured every 15 min for 4 h. Administration of LPS continuously decreased HR, BP, RBF and UV. KW-3902, furosemide or their corresponding vehicle was given as a bolus injection 5 min after the LPS injection. Treatment with KW-3902 (1 mg/kg, i.v.) ameliorated the LPS-induced decline of UV and RBF. Furosemide (3.2 mg/kg, i.v.) tended to ameliorate the LPS-induced decline of UV but not RBF, the duration of the effect being shorter than that of KW-3902. These results suggest that KW-3902 can ameliorate the oliguria and the decrease in RBF during the early phase of LPS-induced shock. Endogenous adenosine may be involved in the endotoxin-induced oliguria via the adenosine A1-receptor.

Animals↗
PubMed1999

[Effects of benidipine hydrochloride (Coniel) on blood pressure, heart rate and plasma norepinephrine concentration in spontaneously hypertensive rats].

We investigated the effects of benidipine hydrochloride (benidipine, Coniel) on blood pressure, heart rate and plasma norepinephrine (NE) concentration in spontaneously hypertensive rats and compared them with those of other calcium channel blockers. Benidipine (2 mg/kg, p.o.) was compared with the equihypotensive doses of nifedipine (5 mg/kg), cilnidipine (6 mg/kg) and amlodipine (3 mg/kg). All the 4 calcium channel blockers exhibited significant antihypertensive effects. Nifedipine and cilinidipine significantly increased heart rate, as compared with that in the control group, whereas benidipine or amlodipine did not significantly affect it. The area under the curves for hypotensive effect and tachycardic effect for 10 hr after the drug administration were compared among the 4 compounds. As a result, the tachycardic effect of benidipine was significantly lower than those of nifedipine, cilnidipine and amlodipine, while the hypotensive effects were similar among the 4 compounds. Nifedipine and amlodipine, significantly increased plasma NE concentration, cilnidipine tended to increase it. In contrast, benidipine did not significantly affect plasma NE concentration. These results suggest that the effects of benidipine on plasma NE concentration and heart rate are less prominent than those of the other calcium channel blockers.

Amlodipine↗