Biomedical subjects

C Kamei

Publications and source records attributed to C Kamei.

At least 55 records · Page 3Linked to original sources

PubMed1999

Effect of propolis extract on D-galactosamine-induced hepatic injury in rats.

The preventive effect of propolis extract on D-galactosamine-induced hepatic injury was examined in rats. Serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) activities were significantly increased at 24 h after intraperitoneal injection of D-galactosamine (400 mg/kg) in the animals. Propolis extract was administered orally three times in doses of 3 or 30 mg/kg at 18 h and 1 h before and 8 h after D-galactosamine injection. The extract itself and the vehicle alone (dextran) caused no significant changes in serum AST or ALT activities. Treatment with the extract dose-dependently prevented the increases in serum AST and ALT activities induced by D-galactosamine, and significant inhibition was observed at a dose of 30 mg/kg. These results suggested that propolis extract may have an ameliorating effect on hepatic dysfunction.

Alanine Transaminase↗

PubMed1999

Synthesis and pharmacological activity of 4-amino-5-chloro-2-methoxy-N-[(2S,4S)-1-ethyl-2-hydroxymethyl-4- pyrrolidinyl]benzamide (TKS159) and its optical isomers.

Of 4-amino-5-chloro-2-methoxy-N-(1-ethyl-2-hydroxymethyl-4- pyrrolidinyl)benzamide, four optical isomers, (2S,4S)-1 (TKS159), (2S,4R)-25, (2R,4S)-26 and (2R,4R)-27, were prepared from optically active 4-amino-1-ethyl-2-hydroxymethylpyrrolidine di-p-toluenesulfonate [(2S,4S)-14, (2S,4R)-17, (2R,4S)-20 and (2R,4R)-23, respectively]. The requisites, (2S,4S)-14, (2S,4R)-17, (2R,4S)-20 and (2R,4R)-23, were prepared from a commercially available trans-4-hydroxy-L-proline. The absolute configurations of (2S,4S)-1 (TKS159), (2S,4R)-25, (2R,4S)-26 and (2R,4R)-27 were spectroscopically determined. Of the benzamide derivatives, four optical isomers, (2S,4S)-1, (2S,4R)-25, (2R,4S)-26 and (2R,4R)-27, showed a relatively potent affinity for 5-hydroxytryptamine 4 (5-HT4) receptors in a radioligand binding assay ([3H]GR113808). The activities of 25-27 were less effective than that of 1 for the gastric emptying of a phenol red semisolid meal in rats. All this suggests that the most potent of the isomers was 4-amino-5-chloro-2-methoxy-N-[(2S,4S)-1-ethyl-2- hydroxymethyl-4-pyrrolidinyl]benzamide (1).

Animals↗

PubMed1999

Effects of certain cerebral circulation activating drugs on regional cerebral blood flow in rats.

The effects of certain cerebral circulation activating drugs on regional cerebral blood flow (rCBF) in the frontal cortex (FCOR), hippocampus (HPC) and nucleus caudatus (CAD) were investigated using the hydrogen clearance method in rats. All the drugs used in the present study, i.e., ozagrel, ifenprodil, pentoxifylline, cinnarizine and dilazep, caused an increase in rCBF in the FCOR, HPC and CAD. Ozagrel was the most potent in increasing rCBF at the FCOR. Ozagrel, ifenprodil, cinnarizine and dilazep were more effective than pentoxifylline in increasing rCBF at the HPC. On the other hand, all the drugs showed almost the same potency in increasing rCBF at the CAD. These results suggested that measurement of rCBF is useful for estimating the efficacy of cerebral circulation activating drugs.

Anesthesia↗

PubMed1999

Effects of fujibitol, a remedy for nasal symptoms of immediate and delayed type allergic reactions.

The effects of Fujibitol, a remedy for the nasal symptoms of immediate and delayed type allergic reactions were studied. Fujibitol inhibited active systemic anaphylaxis in mice, heterologous passive cutaneous anaphylaxis (PCA) in rats, Masugi's nephritis in rats and delayed type hypersensitivity induced by picryl chloride in mice, but did not affect homologous PCA or immune complex-induced glomerulonephritis in rats. These results suggested that Fujibitol is effective for treatment of allergy-induced inflammation since IgG and type IV allergic reactions were inhibited.

Anaphylaxis↗

PubMed1999

Effects of levocabastine on lipid mediator release from guinea pig lung fragments.

The effects of levocabastine, a novel histamine H1-receptor antagonist, on lipid mediator release induced by antigen-antibody reaction from actively sensitized guinea pig lung fragments were studied. Levocabastine dose-dependently inhibited the release of leukotriene C4 from guinea pig lung fragments induced by antigen. A significant effect was observed with levocabastine at a concentration of 10(-4) M. On the other hand, levocabastine produced no effect on the release of leukotriene E4 or thromoboxane B2. From these findings, it was concluded that levocabastine may be useful for relieving the nasal obstruction in allergic rhinitis caused by inhibition of leukotriene C4 release.

Animals↗

PubMed1999

Effects of histamine and related compounds on regional cerebral blood flow in rats.

The effects of histamine and related compounds on regional cerebral blood flow (rCBF) in the hippocampus of conscious rats were studied. Intracerebroventricular injection of histamine caused a dose-dependent increase in rCBF in the hippocampus, and similar findings were observed with not only the H1 agonist, 2-thiazolylethylamine, but also the H2 agonist, dimaprit. Intraperitoneal injection of L-histidine also resulted in an increase in rCBF in the hippocampus, in parallel with elevation of histamine content in the brain. The increase in rCBF in the hippocampus induced by L-histidine was antagonized by both H1 and H2 antagonists (diphenhydramine, pyrilamine and zolantidine). In addition, when both antagonists were injected simultaneously, an additive effect was observed in antagonism of the L-histidine-induced increase in rCBF. L-Histidine caused no marked changes in blood pressure even at a dose of 1,500 mg/kg, which showed an increase in rCBF in the hippocampus. These results indicate that histamine elicited an increase in rCBF via both H1 and H2 receptors.

Animals↗

PubMed1998

The effects of histamine H3-receptor antagonists on amygdaloid kindled seizures in rats.

The effects of histamine H3-receptor antagonists, thioperamide, and clobenpropit on amygdaloid kindled seizures were investigated in rats. Both intracerebroventricular (i.c.v.) and intraperitoneal (i.p.) injections of H3-antagonists resulted in a dose-related inhibition of amygdaloid kindled seizures. An inhibition induced by thioperamide was antagonized by an H3-agonist [(R)-alpha-methylhistamine] and H1-antagonists (diphenhydramine and chlorpheniramine). On the other hand, an H2-antagonist (cimetidine and ranitidine) caused no antagonistic effect. Metoprine, an inhibitor of N-methyltransferase was also effective in inhibiting amygdaloid kindled seizure, and this effect was augmented by thioperamide treatment.

Amygdala↗

PubMed1998

Effects of histamine H1 receptor antagonists on compound 48/80-induced scratching behavior in mice.

The effects of histamine H1 receptor antagonists on compound 48/80-induced scratching behavior were studied in mice. Classical histamine H1 receptor antagonists such as diphenhydramine and chlorpheniramine caused a potent depressant effect on compound 48/80-induced scratching behavior. Histamine H1 receptor antagonists having antiallergic activity (an inhibition of mast cell degranulation), such as azelastine and oxatomide and nonsedative histamine H receptor antagonists such as terfenadine, epinastine and astemizole, also showed a relatively potent effect. On the other hand, the effects of tranilast and cromolyn sodium--antiallergic drugs without histamine H1 receptor antagonistic activity--were extremely weak. Diazepam had weak or no depressant effects on compound 48/80-induced scratching behavior. These results suggest that inhibition of compound 48/80-induced scratching behavior is mainly due to histamine H1 receptor antagonistic activity and not to the sedative action of the drugs.

Animals↗

PubMed1998

Strain differences in histamine release from peritoneal mast cells in rats.

1. Peritoneal mast cells from Brown-Norway (BN) rats were compared with those from Wistar and Sprague-Dawley (SD) rats. 2. Peritoneal mast cells from BN rats showed the smallest values in number, cell diameter and histamine contents compared with those from Wistar and SD rats. 3. BN rat peritoneal mast cells were more sensitive to compound 48/80 and anti-IgE than were those from Wistar and SD rats, and they showed a higher response to A23187 than did cells from Wistar rats. 4. The histamine release from passively sensitized peritoneal mast cells was weaker in BN rats than was that from Wistar and SD rats.

Animals↗

PubMed1998

Histaminergic mechanisms in amygdaloid-kindled seizures in rats.

The present study was undertaken to clarify the role of histaminergic neuron system on amygdaloid kindled seizures in rats. A significant decrease in histamine contents in the amygdala was observed after development of amygdaloid kindling. Histidine and metoprine inhibited amygdaloid kindled seizures at doses causing an increase in histamine contents of the brain. H1-antagonists (diphenhydramine and chlorpheniramine) attenuated histidine-induced inhibition of amygdaloid kindled seizures, however no significant antagonism was observed with H2-antagonists (zolantidine and ranitidine). The development of amygdaloid kindling was retarded by repeated administration of histidine. These findings suggest that histaminergic mechanisms play a suppressive role in amygdaloid kindled seizures through histamine H1-receptors.

Amygdala↗

PubMed1998

Anticonvulsant properties of 1,4-benzodiazepine derivatives in amygdaloid-kindled seizures and their chemical structure-related anticonvulsant action.

The effects of 14 different 1,4-benzodiazepines on amygdaloid-kindled seizures and their chemical structure-related anticonvulsive actions were studied. The prophylactic effects of 1, 4-benzodiazepines on amygdaloid-kindled seizures were also examined. Male Wistar strain rats were used in this study. Rats were anesthetized with pentobarbital sodium (35 mg/kg i.p.) and bipolar electrodes were implanted into the right amygdala. The stimulating parameters were 1 ms pulse duration, 60 Hz frequency and a 1 s duration at an intensity just sufficient to induce afterdischarge (AD). All the 1,4-benzodiazepines depressed both seizure stage and AD duration of amygdaloid-kindled seizures. Of the 1, 4-benzodiazepines, prazepam, flutoprazepam and flurazepam with a long alkyl chain at position 1 were less effective than the drugs having a hydrogen or methyl group at the same position. Nitrazepam, nimetazepam, flunitrazepam and clonazepam which have a nitro group at position 7 showed more potent antiepileptic activity than the drugs with a chloro group. Certain 1,4-benzodiazepines caused inhibition of the development of amygdaloid-kindled seizures. The existence of a hydrogen or methyl group at position 1 and a nitro group at position 7 is important for exhibiting potent anticonvulsant activity in amygdaloid-kindled seizures. Introduction of an oxygen group at position 2 is also necessary for high activity. 1,4-benzodiazepines had not only therapeutic but also prophylactic effects on amygdaloid-kindled seizures.

Amygdala↗

PubMed1998

Characterization of ASK mice, a strain highly sensitive to anaphylactic shock.

A mouse strain named ASK that was originally isolated from El (epilepsy) mice has been shown to be highly sensitive to anaphylactic shock. Here, we characterized the bases of the sensitivity of ASK mice in comparison with the parental strain, El. More than 90% of ASK mice, but not El mice that had been sensitized either actively or passively, died within 1 h following an antigen challenge. The anaphylactic death was effectively blocked by diphenhydramine. Plasma histamine levels increased by 30-50 fold in ASK after the antigen challenge, but only a 2-3-fold increase was observed in El mice. All (El x ASK) F1 mice, either male or female, showed an ASK-like phenotype, suggesting that the impaired plasma histamine response in El mice is due to some recessive mutation(s). Consistent with the plasma histamine responses, cultured mast cells derived from El bone marrow showed impaired potency to degranulate in response to surface IgE engagement, in contrast to ASK mast cells which undergo normal degranulation. Another characteristic feature of ASK mice is their sensitivity to histamine, since 75% of the mice were killed by the subcutaneous administration of 100-200 mg/kg histamine, while C3H and BALB/c mice were resistant to even 600 mg/kg histamine. Taken together, the major bases of the susceptibility to anaphylactic shock in ASK mice are thought to be the enhanced sensitivity to histamine and the recovered degranulation machinery in mast cells that is impaired in El mice.

Anaphylaxis↗

PubMed1998

Effect of methylcarbonylmethyl 2(S)-[4-(4-guanidino-benzoyloxy)phenyl] propionate methanesulfonate (TT-S24) on experimental pancreatitis in rats.

The effect of methylcarbonylmethyl 2(S)-14-(4-guanidino-benzoyloxy) phenyl] propionate methanesulfonate (TT-S24) on experimental pancreatitis in rats was examined in comparison with that of camostat. TT-S24 showed a preventive effect on increases in plasma amylase activity and pancreatic weight induced by cerulein injection. TT-S24 also reduced an increase in plasma amylase activity induced by taurocholate. TT-S24 effectively prevented the mortality induced by an injection of a mixture of trypsin and taurocholate. TT-S24 showed no effect on an increase in amylase activity 6 h after duodenum ligation (closed duodenal loop pancreatitis), indicating that the drug had no effect on the initiation and propagation step of closed duodenal loop pancreatitis. On the other hand, TT-S24 reduced an increase in amylase activity 6 h after release of the duodenum ligation. TT-S24 showed anti-trypsin, anti-kallikrein, anti-thrombin and anti-plasmin activities. The effect of TT-S24 on some experimental pancreatitis models was nearly equal to or somewhat more potent in most instances to that of camostat. Therefore, TT-S24 should be useful in the clinical treatment of pancreatitis.

Amylases↗

PubMed1998

Effects of ethanol, acetoin and 2,3-butanediol on EEG power spectra in conscious rats.

Effects of ethanol, acetoin and 2,3-butanediol on the central nervous system (CNS) were investigated by using the analysis of EEG (electroencephalogram) spectral powers recorded at the frontal cortex in rats. High doses of ethanol were required for exhibiting an increase of EEG spectral powers in the delta (0-4 Hz) and theta (4-8 Hz) waves when it was given either orally or intravenously. On the other hand, when ethanol was injected intracerebroventricularly, the drug caused a potent increasing effect of EEG spectral powers. Both acetoin and 2,3-butanediol were found to increase in EEG spectral powers by oral and intravenous administrations at relatively low doses. In addition, acetoin and 2,3-butanediol were more effective than ethanol in increasing EEG spectral powers in the delta and theta bands after intracerebroventricular administration. From these findings it can be concluded that both acetoin and 2,3-butanediol have a potent CNS depressant effect.

Acetoin↗

PubMed1998

Effect of methylcarbonylmethyl 2(S)-[4-(4-guanidinobenzoyloxy) phenyl] propionate methanesulfonate (TT-S24) on pancreatic secretion in rats.

The effect of methylcarbonylmethyl 2(S)-[4-(4-guanidinobenzoyloxy) phenyl] propionate methanesulfonate (TT-S24), a newly synthesized trypsin inhibitor, on exocrine pancreatic secretion was examined and compared with that of camostat in rats. Intraduodenal (i.d.) administration of TT-S24 and camostat resulted in an increase in volume, amylase concentration and amylase output of pancreatic juice. Although i.v. injection of TT-S24 and camostat (3 mg/kg) had no effect on the pancreatic juice volume, TT-S24 (i.v.) dose-dependently increased pancreatic juice volume under acetylcholine (10 micrograms/kg/min) infusion. In addition, the weight of pancreases from WBN rats was significantly increased by 28 day oral administration of TT-S24 (100 mg/kg) with a potency similar to that observed with camostat.

Acetylcholine↗

PubMed1998

Effects of certain resorcinol derivatives on the tyrosinase activity and the growth of melanoma cells.

Effects of certain resorcinol derivatives on tyrosinase activity, melanin formation and some other biological activities were studied in order to develop a new, potent depigmentor and/or antimelanoma drug. NKO-09, having isopentyl group in position 6 of resorcinal, exhibited a more potent effect than the compounds which have methyl (NKO-10), ethyl (NKO-11), hexyl (KOM-14), octyl (NKO-14), decyl (NKO-19), dodecyl (NKO-15) and tetradecyl (NKO-16) group in inhibiting the tyrosinase activities (both tyrosine hydroxylation and dopa oxidation). NKO-09 was more potent than hydroquinone in inhibiting the tyrosine hydroxylation; furthermore, NKO-09 inhibited the dopa oxidation different from hydroquinone. In the studies on melanin formation, protein synthesis and the growth of the melanoma cells, NKO-09 caused the most potent effect among the test compounds, except for the growth of the melanoma cells. KOM-14 was more potent than NKO-09 in the antimelanoma activity, and its effect was superior than that of 5-fluorouracil. From these findings, it is suggested that NKO-09 and KOM-14 can be used as an efficacious depigmentor and antimelanoma drug, respectively.

Animals↗

PubMed1997

Histamine-induced cortisol secretion from bovine adrenocortical cells: co-incubated with bovine adrenal medullary cells.

Histamine at concentrations higher than 10(-9) M significantly elicited cortisol secretion from bovine adrenocortical (BAC) cells co-incubated with bovine adrenal medullary (BAM) cells, suggesting that BAM cells are responsible for histamine-induced cortisol secretion. Cortisol secretion from BAC cells co-incubated with BAM cells was also elicited by both an H1 agonist, 2-methylhistamine, and an H2 agonist, 4-methylhistamine. However, 4-methylhistamine was much less effective than 2-methylhistamine. Histamine-induced cortisol secretion was inhibited not only by H1 antagonists (pyrilamine and diphenhydramine) but also by H2 antagonists (cimetidine and ranitidine). Histamine effectively increased 45Ca uptake and IP3 production in BAM cells. These responses were antagonized by the H1 antagonist but not by the H2 antagonist. Histamine-induced cortisol secretion from BAC cells co-incubated with BAM cells was inhibited by beta-adrenoceptor antagonists, propranolol and timolol, as well as an NK1-receptor antagonist, D-Arg1-D-Trp7,9-Leu11-substance P. These results indicate that histamine can induce cortisol secretion from BAC cells at physiological concentrations through H1 receptors on BAM cells, and catecholamine and substance P may participate in histamine-induced cortisol secretion.

Adrenal Cortex↗

PubMed1997

Effect of an active metabolite of the antiallergic agent tazanolast on histamine release from rat mast cells.

WP-871 (3'-(1H-tetrazol-5-yl)oxanilic acid monohydrate, CAS 114607-46-4) is a monohydrate of a main active metabolite of tazanolast (butyl 3'-(1H-tetrazol-5-yl) oxanilate, CAS 82989-25-1), an orally active antiallergic drug. WP-871 inhibited dose-dependently compound 48/80-induced histamine release from rat peritoneal mast cells. In a similar dose range, WP-871 was effective in inhibiting compound 48/80-induced 45Ca uptake into mast cells from extracellular medium and compound 48/80-induced translocation of protein kinase C from the cytosol to the membrane fraction of mast cells. WP-871 also inhibited inositol trisphosphate production but did not exhibit a direct inhibitory effect on phospholipase C in mast cells. WP-871 caused no increase in cAMP content in mast cells. These results suggest that WP-871 may inhibit histamine release mainly by preventing the increase in intracellular Ca2+ concentration, which is a critical event in signal transduction leading to histamine release in mast cells.

Animals↗