日本薬学会Acta Medica Okayama0918615831112008Royal jelly ameliorates insulin resistance in fructose-drinking rats21032107ENYoshitoZamamiShingoTakatoriMitsuhiroGodaToshihiroKoyamaYukikoIwataniXinJinShimaTakada-DoiHiromuKawasakiRoyal jelly (RJ) is known to contain excellent nutrition and a variety of biological activities. The present study was designed to investigate the effects of RJ on insulin resistance (hyperinsulinemia) in fructose-drinking rats (FDR; insulin resistance animal model). Male Wistar rats (6 weeks old) received 15% fructose solution in drinking water for 8 weeks. FDR showed significant increases in plasma levels of insulin and triglyceride, Homeostasis Model Assessment ratio (HOMA-R, an index of insulin resistance), and systolic blood pressure, but not blood glucose levels, when compared with control rats. RJ (100, 300mg/kg, p.o.) treatment for 8 weeks significantly decreased the plasma levels of insulin and triglyceride, HOMA-R, without affecting blood glucose or total cholesterol levels and tended to lower systolic blood pressure. In isolated and perfused mesenteric vascular beds of FDR, RJ treatment resulted in a significant reduction in sympathetic nerve-mediated vasoconstrictor response to periarterial nerve stimulation (PNS) and tended to increase the calcitonin gene-related peptide (CGRP) nervemediated vasodilator response to PNS, compared with those in untreated FDR. However, RJ treatment did not significantly affect norepinephrine-induced vasoconstriction or CGRP-induced vasodilation. These results suggest that RJ could be an effective functional food to prevent insulin resistance associated with the development of hypertension.No potential conflict of interest relevant to this article was reported.日本薬学会Acta Medica Okayama00316903127122007フルクトース負荷インスリン抵抗性モデル(ラット)におけるPropolisによるインスリン抵抗性改善作用20652073ENYoshitoZamamiShingoTakatoriToshihiroKoayamaMitsuhiroGodaYukikoIwataniShimaDoiHiromuKawasakiPropolis, a honeybee product, contains a variety of biologically active substances. The present study was designed to investigate the effects of propolis on insulin resistance induced by fructose-drinking rats (FDR; type 2 diabetic animal model). Male Wistar rats (6 weeks old) received 15% fructose solution in drinking water for 8 weeks. FDR showed significant increases in plasma levels of insulin, Homeostasis Model Assessment ratio (HOMA-R, an index of insulin resistance), body weight, and systolic blood pressure but not blood glucose levels, when compared with control rats. Brazilian propolis extract (100 and 300mg/kg, p. o.) treatment for 8 weeks significantly decreased the plasma level of insulin, HOMA-R, and body weight, increased plasma triglyceride levels without affecting blood glucose and total cholesterol levels, and tended to decrease systolic blood pressure. In isolated and perfused mesenteric vascular beds of FDR, propolis treatment resulted in a significant reduction of sympathetic nerve-mediated vasoconstrictor response to periarterial nerve stimulation (PNS; 8Hz) and tended to increase the calcitonin gene-related peptide (CGRP) nerve-mediated vasodilator response to PNS, compared with those in untreated FDR. However, propolis treatment did not significantly affect norepinephrine-induced vasoconstriction and CGRP-induced vasodilation. These results suggest that propolis could be an effective functional food to prevent the development of insulin resistance.No potential conflict of interest relevant to this article was reported.日本薬学会Acta Medica Okayama0031690312832008食後高血糖が血管反応性に及ぼす影響419424ENYoshitoZamamiShingoTakatoriYukikoIwataniKosukeYamawakiSatokoMiyashitaNanaYabumaeFusakoTakayamaMitsunobuMioHiromuKawasakiRecent clinical studies demonstrated that transient postprandial hyperglycemia and hyperinsulinemia may contribute to the development of hypertension. Therefore, we investigated influence of acute hyperglycemia and/or hyperinsulinemia induced by glucose or insulin infusion on neuronal and humoral control of vascular tone in rats. Euglycemic male Wistar rats were pithed under anesthesia and arterial blood pressure was measured. Changes in vascular responses to spinal cord stimulation (SCS) and intravenous bolus injections of noradrenaline, angiotensin II, calcitonin generelated peptide (CGRP), acetylcholine and sodium nitroprusside (SNP) were studied by infusing various concentration of glucose or insulin. Continuous glucose infusion, which increased both blood glucose and serum insulin levels, significantly augmented adrenergic nerve-mediated pressor responses to SCS without affecting injection of pressor responses to noradrenaline or angiotensin II. In pithed rats with artificially increased blood pressure and blockade of autonomic outflow, glucose infusion attenuated CGRPergic nerve-depressor responses to SCS without affecting depressor responses to injection of CGRP, acetylcholine or SNP. In pithed rats treated with octreotide, which increased blood glucose without increasing serum insulin levels, glucose infusion caused only significant augmentation of adrenergic nervemediated pressor responses. Combined infusion of insulin and glucose, which resulted in increased serum insulin levels with euglycemic, significantly augmented adrenergic nerve-mediated pressor responses and attenuated CGRPergic nerve-mediated depressor responses. The present results suggest that acute hyperglycemia and hyperinsulinemia increases adrenergic nerve-mediated vasoconstriction, which is partly associated with the blunted CGRPergic nerve function, and that plasma insulin concentration associated with hyperglycemia may be responsible for alteration of neuronal vascular regulation.No potential conflict of interest relevant to this article was reported.日本薬学会Acta Medica Okayama0031-690313062010Propolis 長期投与による Otsuka Long-Evans Tokushima Fatty (OLETF) ラットの インスリン抵抗性改善作用833840ENYoshitoZamamiHirokiFujiwaraMihoHosodaHayatoHinoKazuhiroHiraiKazuakiOkamotoHiromuKawasakiPropolis is known to have abundant bioactive constituents and a variety of biological activities. To investigate the effect of Brazilian propolis on insulin resistance, 10-week-old Otsuka Long-Evans Tokushima Fatty (OLETF) rats, a non-insulin-dependent type 2 diabetic model, were treated for 4 weeks with propolis (100 and 300 mg/kg, p.o.) or vehicle (control). Propolis treatment significantly decreased the plasma levels of insulin and insulin resistance index (Homeostasis Model Assessment-Insulin Resistance; HOM-IR), without affecting blood glucose levels and tended to lower systolic blood pressure compared with the control. In isolated and perfused mesenteric vascular beds of OLETF rats, propolis treatment resulted in significant reduction of sympathetic nerve-mediated vasoconstrictor response to periarterial nerve stimulation (PNS) and tended to increase calcitonin gene-related peptide (CGRP) nerve-mediated vasodilator response to PNS compared with in vehicle-treated OLETF rats. However, propolis treatment did not significantly affect the vasoconstrictor and vasodilator response to noradrenaline, CGRP, acetylcholine, and sodium nitroprusside. These results suggest that propolis could be an effective and functional food to prevent development of insulin resistance.No potential conflict of interest relevant to this article was reported.Okayama University Medical SchoolActa Medica Okayama0386-300X6442010Effects of Imipramine and Lithium on the Suppression of Cell Proliferation in the Dentate Gyrus of the Hippocampus in Adrenocorticotropic Hormone-treated Rats219223ENMahoDoiIkukoMiyazakiTomokoNagamachiKazuakiShinomiyaHisashiMatsunagaToshiakiSendoHiromuKawasakiMasatoAsanumaYutakaGomitaYoshihisaKitamuraOriginal Article10.18926/AMO/40129We examined the influence of chronic adrenocorticotropic hormone (ACTH) treatment on the number of Ki-67-positive cells in the dentate gyrus of the hippocampus in rats. ACTH treatment for 14 days decreased the number of such cells. The administration of imipramine or lithium alone for 14 days had no effect in saline-treated rats. The effect of ACTH was blocked by the administration of imipramine. Furthermore, the coadministration of imipramine and lithium for 14 days significantly increased the number of Ki-67-positive cells in both the saline and ACTH-treated rats. The coadministration of imipramine and lithium normalized the cell proliferation in the dentate gyrus of the hippocampus in rats treated with ACTH.No potential conflict of interest relevant to this article was reported.Acta Medica Okayama3432008Evaluation of intramuscular lateral distribution profile of topically administered acetaminophen in ratsENYujiKurosakiMasahiroTagawaAkihoOmotoHiroshiSuitoYukikoKomoriHiromuKawasakiTetsuyaAiba<p>To clarify to what extent topically administered drug molecules horizontally permeate into tissues surrounding the administration site, the intramuscular lateral concentration profile of acetaminophen was investigated in vivo using the microdialysis method in rats. When acetaminophen was intramuscularly administered for 6 hr in a pinpoint manner at a constant rate of 3 μg/min, it was clearly detected in the muscle surrounding the administration site, being 17.5 μg/ml when measured at a 2 mm distance from the administration site. The concentration in the muscle was decreased as the distance increased, and those measured at 5 mm and 40 mm were 0.35 μg/ml and 0.09 μg/ml, respectively. In addition, it was shown that the concentration in the muscle at 40 mm reflected the compound’s concentration in plasma, but not the compound’s horizontal
permeation from the administration site. With these observations, the intramuscular distribution profile of acetaminophen was numerically characterized according to Fick’s law. As a result, it was revealed that horizontal permeation is the primary process accountable for the increased intramuscular concentration only in the area adjacent to the administration
site, and the radius of the adjacent area was calculated to be 5.80 mm for acetaminophen. </p>
No potential conflict of interest relevant to this article was reported.Acta Medica Okayama8932008Chronic coadministration of carbamazepine together with imipramine produces antidepressant-like effects in an ACTH-induced animal model of treatment–resistant depression: Involvement of 5-HT 2A receptors?ENYoshihisaKitamuraKozueAkiyamaKouheiKitagawaKazuhikoShibataHiromuKawasakiKatsuyaSuemaruHiroakiArakiToshiakiSendoYutakaGomita<p>The use of carbamazepine has been reported to be an effective treatment for severe depression. We have already shown that the antidepressant-like effects of tricyclic antidepressants in the rat forced swim test (FST) are blocked by chronic treatment with adrenocorticotropic hormone (ACTH). In the present study, we examined the effect of the chronic administration of carbamazepine on the FST and the wet-dog shakes induced by (+/-)-1-(2,5-dimethoxy-4-iodophenyl)-2-aiminopropane (DOI), a 5-HT2A receptor agonist, in ACTH-treated rats. Chronic administration of carbamazepine did not affect the duration of immobility in saline-treated and ACTH-treated rats. The reduction of immobility, induced by chronic administration of imipramine, was blocked by treatment with ACTH. When carbamazepine was administered concurrently with imipramine, we observed a significant decrease in immobility in rats treated with ACTH. Chronic ACTH treatment increased the number of the wet-dog shakes induced by DOI. This effect of ACTH was significantly increased by the coadministration of carbamazepine and imipramine. These results suggest that the use of carbamazepine together with tricyclic antidepressants had the effect of reducing immobility time in the FST in a tricyclic antidepressant-treatment-resistant depressive model induced by chronic ACTH treatment. </p>
No potential conflict of interest relevant to this article was reported.Acta Medica Okayama15032008Angiotensin II type 2 receptors facilitate reinnervation of phenol-lesioned vascular calcitonin gene-related peptide (CGRP)-containing nerves in rat mesenteric arteries730741ENNarumiHobaraMitsuhiroGodaNamikaYoshidaShingoTakatoriYoshihisaKitamuraMitsunobuMioHiromuKawasaki<p>The present study was designed to investigate involvement of angiotensin (Ang) II type 2 receptors (AT2 receptors) in restoration of perivascular nerve innervation injured by topical phenol treatment. Male Wistar rats underwent in vivo topical application of 10% phenol around the superior mesenteric artery. After phenol treatment, animals were subjected to immunohistochemistry of the third branch of small arteries, Western blot analysis of AT2 receptor protein expression in dorsal root ganglia (DRG) and studies of mesenteric neurogenic vasoresponsiveness. Ang II (750 ng/kg/day), nerve growth factor (NGF; 20 μg/kg/day) and PD123,319 (AT2 receptor antagonist; 10 mg/kg/day) were intraperitoneally administered for 7 days using osmotic mini-pumps immediately after topical phenol treatment. Losartan (AT1 receptor antagonist) was administered in
drinking water (0.025%). Phenol treatment markedly reduced densities of both calcitonin gene-related peptide (CGRP)-like immunoreactivity (LI)- and neuropeptide Y (NPY)-LI-containing fibers. NGF restored densities of both nerve fibers to the Sham control level. Coadministration of Ang II and losartan significantly increased the density of CGRP-LI-fibers but not
NPY-LI-fibers compared with saline control. The increase of the density of CGRP-LI-fibers by coadministration of Ang II and losartan was suppressed by adding PD123,319. Coadministration of Ang II and losartan ameliorated reduction of CGRP nerve-mediated vasodilation of perfused mesenteric arteries caused by phenol treatment. The AT2 receptor protein expression detected in DRG was markedly increased by NGF. These results suggest that selective stimulation of AT2 receptors by Ang II facilitates reinnervation of mesenteric perivascular CGRP-containing nerves injured by topical phenol application in the rat.</p>No potential conflict of interest relevant to this article was reported.Okayama University Medical SchoolActa Medica Okayama0386-300X6162007The Influence of Hyperactivity of the Hypothalamic-pituitary-adrenal Axis and Hyperglycemia on the 5-HT2A Receptor-mediated Wet-dog Shake Responses in Rats311317ENYuichiUmedaManabuAmanoKatsuyaSuemaruTakumiYamaguchiYoshihisaKitamuraYutakaGomitaHiromuKawasakiHiroakiArakiOriginal Article10.18926/AMO/32879<p>Hyperactivity of the hypothalamic-pituitary-adrenal (HPA) axis induces hyperglycemia and serotonin (5-HT)2A receptor supersensitivity. In the present study, to investigate the effect of hyperglycemia on the function of 5-HT2A receptors, we compared the 5-HT2A receptor-mediated wet-dog shake responses in rats treated with adrenocorticotropic hormone (ACTH), dexamethasone and streptozotocin. ACTH (100 μg/rat per day, s.c.), dexamethasone (1 mg/kg per day, s.c.) and streptozotocin (60 mg/kg, i.p.) produced significant hyperglycemia at 14 days after the start of these treatments, and the hyperglycemia was most pronounced in the streptozotocin-treated rats. The wet-dog shake responses induced by (±)-1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI), a 5-HT2A receptor agonist, were significantly enhanced at 14 days after repeated treatment with ACTH and dexamethasone. However, streptozotocin-induced diabetes had no effect on the wet-dog shake responses. The results of the present study suggest that hyperglycemia is not strongly associated with the enhanced susceptibility of 5-HT2A receptors under the condition of hyperactivity of the HPA axis.</p>No potential conflict of interest relevant to this article was reported.Okayama University Medical SchoolActa Medica Okayama0386-300X6142007Effects of Physical and Psychological Stress on 5-HT2A Receptor-mediated Wet-dog Shake Responses in Streptozotocin-induced Diabetic Rats.205212ENManabuAmanoKatsuyaSuemaruRanjiCuiYuichiUmedaBingjinLiYutakaGomitaHiromuKawasakiHiroakiArakiOriginal Article10.18926/AMO/32870Several epidemiological and clinical studies have indicated that the prevalence of psychiatric disorders is higher in diabetic patients than in the general population. In the present studies, we examined the behavioral changes in streptozotocin-induced diabetic rats, and investigated the effects of physical and psychological stress on the hippocampal BDNF levels and on the serotonin 2A (5-HT2A) receptor-mediated wet-dog shake responses. The streptozotocin (60 mg/kg, i.p.)-induced diabetes had no significant effects on the immobility time in the forced swim test or on locomotor activity in the open-field test. Moreover, there was no significant difference in the wet-dog shake responses induced by DOI, a 5-HT2A receptor agonist, between nondiabetic and diabetic rats. Five-day exposure to physical (electric footshock) and psychological (non-footshock) stress had no signifi cant effect on the hippocampal BDNF level in diabetic or nondiabetic rats. The 2 types of stress had no significant effect on the DOI-induced wet-dog shake responses in nondiabetic rats. In diabetic rats, the repeated exposure to physical stress markedly increased the DOI-induced wet-dog shake responses, but the repeated exposure to psychological stress had no effect. These results suggest that exposure to physical stress augmented the susceptibility to the wet-dog shake responses to 5-HT2A receptor stimulation in streptozotocin-induced diabetic rats.No potential conflict of interest relevant to this article was reported.Okayama University Medical SchoolActa Medica Okayama0386-300X5412000Influence of exposure to new circumstances on pharmacokinetics of plasma drugs concentrations in rats.4548ENYasuhikoHashimotoHiromuKawasakiYutakaGomitaArticle10.18926/AMO/32306<p>The influences of emotional changes induced by being exposed to a new environment on the pharmacokinetics of plasma drug concentration were studied in male Wistar rats. Transfer from a familiar home cage to a new home cage was considered to induce psychological (non-physical) emotional changes. First, nicorandil and zonisamide, drugs that act on the peripheral system and central nervous systems, were used, respectively. Immediately after oral administration of nicorandil (10 mg/kg) or zonisamide (50 mg/kg), the animals were transferred to new home cages. Plasma nicorandil and zonisamide concentrations were determined by high-performance liquid chromatography at 1 and 4 h after administration. Plasma nicorandil concentration in the group transferred to new home cages was significantly decreased relative to levels in the non-transferred control group. However, zonisamide concentrations were unchanged. These findings suggest that the pharmacokinetics of nicorandil, but not those of zonisamide, tend to be influenced by non-physically induced emotional changes.</p>
No potential conflict of interest relevant to this article was reported.Okayama University Medical SchoolActa Medica Okayama0386-300X5552001Dopaminergic neurotransmission triggers ischemia-induced hyperactivity in Mongolian gerbils.277282ENTakahiroYamamotoHiroakiArakiKoujiroFutagamiHiromuKawasakiYutakaGomitaArticle10.18926/AMO/32017<p>It is recognized that sustained ischemia-induced hyperactivity is related to abnormalities in dopamine function. However, it is unclear that dopaminergic neurotransmission triggers such ischemia-induced hyperactivity. Therefore, the relationship between dopaminergic neurotransmission and ischemia-induced hyperactivity was investigated in an animal model using Mongolian gerbils. When haloperidol 2 mg/kg was administered i.p. 30 min after ischemia, the ischemia-induced hyperactivity at 24 h after ischemia was blocked. General behavior was similar to that of sham-operated animals. Haloperidol at doses of 0.1 and 0.2 mg/kg had no effect on locomotor activity in sham-operated animals and decreased ischemia-induced hyperactivity when the drug was administered 24 h after ischemia; these doses did not have any effect on ischemia-induced hyperactivity when the drug was administered 30 min after ischemia. On the other hand, when the animal was confined to a small, restrictive cage for the 24 h period immediately following ischemic injury, locomotor activity at 24 h after ischemia increased. Such behavior also increased in animals when they were returned to their original more permissive cages immediately after ischemia. It is conceivable that the decrease in the level of activity was not related to ischemia-induced hyperactivity. These data suggested that the inhibition of ischemia-induced hyperactivity can be induced by complete blockage of dopaminergic receptors immediately after ischemia.</p>
No potential conflict of interest relevant to this article was reported.Okayama University Medical SchoolActa Medica Okayama0386-300X6352009Effect of Brewer's Yeast-Induced Pyrexia on Aminophylline-Elicited Convulsions in Mice273280ENRikaOchiKatsuyaSuemaruHiromuKawasakiHiroakiArakiOriginal Article10.18926/AMO/31837<p>Theophylline-associated convulsions have been observed most frequently in children with fever, but the mechanism is not fully understood. In this study, we investigated the basic mechanism of aminophylline [theophylline-2-ethylenediamine]-induced convulsions and the effects of Brewer's yeast-induced pyrexia in mice. Diazepam (5-10mg/kg, i.p.), a benzodiazepine receptor agonist, significantly prolonged the onset and significantly decreased the incidence of convulsions induced by aminophylline (350mg/kg, i.p.). However, the gamma aminobutyric acid (GABA)A receptor agonist muscimol (1-4mg/kg, i.p.), the GABAB receptor agonist baclofen (2-4mg/kg, i.p.) and the N-methyl-D-aspartic acid receptor antagonist dizocilpine (0.1-0.3mg/kg, i.p.) failed to protect against the convulsions. 20% Brewer's yeast (0.02ml/g, s.c.) increased body temperature by 1.03, and also significantly shortened the onset and significantly increased the incidence of convulsions induced by aminophylline. The anticonvulsant action of diazepam (2.5-10mg/kg, i.p.) on the convulsions induced by aminophylline was reduced by Brewer's yeast-induced pyrexia. The proconvulsant actions of the GABAA receptor antagonists picrotoxin (3-4mg/kg, i.p.) and pentylenetetrazol (40-60mg/kg, i.p.) were enhanced by Brewer's yeast. These results suggest that the anticonvulsant action of diazepam against aminophylline is reduced by Brewer's yeast-induced pyrexia, and that GABAA receptors are involved in the aggravation of the convulsions by Brewer's yeast in mice.</p>No potential conflict of interest relevant to this article was reported.Okayama University Medical SchoolActa Medica Okayama0386-300X6322009Beneficial effects of Vitis coignetiae Pulliat leaves on nonalcoholic steatohepatitis in a rat model105111ENFusakoTakayamaKazuoNakamotoHiromuKawasakiMitsumasaMankuraToruEgashiraKeijiUekiAzusaHasegawaShigeruOkadaAkitaneMoriOriginal Article10.18926/AMO/31835<p>Vitis coignetiae Pulliat (Yamabudo) is used as a health juice and wine based on the abundant polyphenols and anthocyanins in its fruit. However, it is not known whether the leaves of this plant confer similar benefits. This study investigated the hepatoprotective effects of aqueous extracts from Vitis coignetiae Pulliat leaves (VCPL) in an animal model of nonalcoholic steatohepatitis (NASH). Rats were fed a choline-deficient high-fat diet for four weeks to generate fatty livers. NASH was induced by oxidative stress loading. Ten weeks later, blood and liver samples were collected from anesthetized animals and assessed biochemically, histologically, and histochemically to determine the extent of oxidative stress injury and the overall effects of VCPL. Six-week VCPL extract supplementation reduced serum levels of liver enzymes, decreased CYP2E1 induction, increased plasma antioxidant activities and delayed the progression of liver fibrosis. The findings suggested that VCPL has strong radical-scavenging activity and may be beneficial in preventing NASH progression.</p>No potential conflict of interest relevant to this article was reported.Okayama University Medical SchoolActa Medica Okayama0386-300X5231998Repeated Mazindol and Methamphetamine Administration Produces Cross-Sensitization to Stereotyped Behavior Induced by these Agents in Rats169171ENYasuhiroKawakamiKatsuyaSuemaruHiroakiArakiHiromuKawasakiYutakaGomitaYoshiroTanizakiArticle10.18926/AMO/31331<p>The cross-sensitization to stereotyped behavior between mazindol (MZD) and methamphetamine (MAP) was investigated in rats. MZD (5 and 10 mg/kg/day, p.o.), MAP (5 and 10 mg/kg/day, p.o.) and saline (1 ml/kg, p.o.) were administered once daily for a week. Challenge with MZD (10 mg/kg, p.o.) on the 8th day caused markedly stereotyped behavior in MAP-pretreated group compared with the saline-pretreated control group. MAP (10 mg/kg, p.o.)-induced stereotyped behavior on the 8th day was also greater in MZD-pretreated group rather than the saline-pretreated control group. These results suggest that repeated MZD and MAP administration cross-sensitizes to their stereotype-producing effects.</p>
No potential conflict of interest relevant to this article was reported.Okayama University Medical SchoolActa Medica Okayama0386-300X5231998Steady-state serum concentrations of carbamazepine and valproic acid in obese and lean patients with epilepsy.139142ENKatsuyaSuemaruHiromuKawasakiKanakoYasuharaKazuhisaYaoKatusushiFurunoYasuhiroKawakamiHiroakiArakiYutakaGomitaEijiOkaArticle10.18926/AMO/31328<p>Steady-state serum concentrations of carbamazepine (CBZ) and valproic acid (VPA) were investigated in normal weight (body mass index; BMI 20 to 25), lean (smaller than 20 BMI) and moderately obese subjects (greater than 25 BMI) who received either 400 mg/day of CBZ or 800 mg/day of VPA. The CBZ serum concentration in lean subjects was significantly higher than that in normal weight subjects. However, no significant differences in VPA serum concentration were found between the three groups. The CBZ serum concentration decreased with increases in total body weight, and the VPA serum concentration decreased with increases in ideal body weight. However, both serum concentrations were not correlated with BMI. These results suggest that VPA doses should be calculated using ideal body weight and that degree of obesity may affect CBZ serum concentration rather than VPA serum concentration.</p>
No potential conflict of interest relevant to this article was reported.Okayama University Medical SchoolActa Medica Okayama0386-300X6252008Endothelium-derived Hyperpolarizing Factor (EDHF) Mediates Endothelium-dependent Vasodilator Effects of Aqueous Extracts from Eucommia ulmoides Oliv. Leaves in Rat Mesenteric Resistance Arteries319325ENXinJinYukikoOtonashi-SatohPengyuanSunNaomiKawamuraTakashiTsuboiYasuyoYamaguchiTaroUedaHiromuKawasakiOriginal Article10.18926/AMO/30965<p>The vascular effects of an aqueous extract prepared from the leaves of Eucommia ulmoides Oliv. (ELE), a medicinal herb commonly used in antihypertensive herbal prescriptions in China, were investigated
in rat mesenteric resistance arteries. The mesenteric vascular bed was perfused with Krebs solution and the perfusion pressure was measured with a pressure transducer. In preparations with an intact endothelium and precontracted with 7μM methoxamine, perfusion of ELE (10<sup>-7</sup>-10<sup>-2</sup>mg/ml for 15min) caused a concentration-dependent vasodilatation, which was abolished by chemical removal of the endothelium. The ELE-induced vasodilatation was inhibited by neither indomethacin (INDO, a cyclooxygenase inhibitor) nor N<sup>G</sup>-nitro-L-arginine-methyl ester (L-NAME, a nitric oxide inhibitor). The ELE-induced vasodilatation was significantly inhibited by tetraethylammonium (TEA, a K<sup>+</sup> channel blocker) and 18α-glycyrrhetinic acid (18α-GA, a gap-junction inhibitor), and abolished by high K<sup>+</sup> -containing Krebsʼ solution. Atropine (a muscarinic acetylcholine receptor antagonist) significantly inhibited the vasodilatation induced by ELE at high concentrations. These results suggest that the ELE-induced vasodilatation is endothelium-dependent but nitric oxide (NO)- and prostaglandin I<sub>2</sub> (PGI<sub>2</sub>)-independent, and is mainly mediated by the endothelium-derived hyperpolarizing factor (EDHF) in the mesenteric resistance arteries. Furthermore, the ELE-induced EDHF-mediated response involves the activation of K<sup>+</sup>-channels and gap junctions.</p>No potential conflict of interest relevant to this article was reported.Okayama University Medical SchoolActa Medica Okayama0386-300X5041996Pharmacokinetic Evaluation of Omeprazole Suspension Following Oral Administration in Rats: Effect of Neutralization of Gastric Acid219222ENKazuhideWatanabeNaoyukiMatsukaKatushiFurunoKoheiEtoHiromuKawasakiYutakaGomitaArticle10.18926/AMO/30470<p>In order to evaluate a clinical use of omeprazole suspension, we examined the pharmacokinetics of omeprazole after oral administration in rats. Although the administration of omeprazole suspension buffered by NaHCO3 solution did not produce a significant increase in the area under the concentration-time curve (AUC) value compared with non-buffered group, the administration of NaHCO3 buffer immediately after dosing of omeprazole suspension buffered by NaHCO3 caused a significant increase in the AUC value. These results suggest that the NaHCO3 treatment following the administration of omeprazole buffered suspension effectively decreased the degradation of the compound by gastric acid. Therefore, the successive administration of NaHCO3 solution after the omeprazole dosing seems to be a simple and useful method for the administration to patients who cannot receive tablets.</p>
No potential conflict of interest relevant to this article was reported.Okayama University Medical SchoolActa Medica Okayama0386-300X4951995Effect of cigarette smoke on lipid peroxidation and liver function tests in rats.271274ENKazuhideWatanabeKoehiEtoKatsushiFurunoTakaakiMoriHiromuKawasakiYutakaGomitaArticle10.18926/AMO/30402<p>The effect of cigarette smoke on organ weights, lipid peroxidation and plasma biochemical parameters was investigated in male Wistar rats. Daily exposure (for 20 min twice a day) to cigarette smoke for 27 days caused a significant decrease in liver weight and a significant increase in lung weight. The smoke-exposure group showed increased lipid peroxidation in the liver, but not in the lung. In the smoke-exposure group, the GOT, gamma-GTP, total bilirubin and LDH values were significantly higher than those in the control group, while the plasma glucose value was significantly lower. These results suggest that cigarette smoking might induce liver injury by enhancing lipid peroxidation.</p>
No potential conflict of interest relevant to this article was reported.Okayama University Medical SchoolActa Medica Okayama0386-300X4951995Effect of pregnancy on plasma phenobarbital concentrations in rats.237240ENMasahiroMoriyamaHaruyoDomotoSyoichiYamashitaKatsushiFurunoRyozoOishiHiromuKawasakiYutakaGomitaArticle10.18926/AMO/30398<p>We examined the pharmacokinetics of phenobarbital before and during pregnancy in rats. Animals were divided into four groups: (a) control, (b) pregnant, (c) phenobarbital-treated, and (d) phenobarbital-treated pregnant groups. The increase in body weight of nonpregnant or pregnant rats was not influenced by long-term phenobarbital treatment. Plasma phenobarbital concentrations during the period of long-term phenobarbital treatment with a fixed dosage by body weight were not significantly affected by pregnancy. Furthermore, pregnancy did not affect pharmacokinetic parameters of phenobarbital between 0.25 and 24h after administration. These results suggest that pregnancy does not influence on the pharmacokinetics of long-term phenobarbital treatment at a fixed dosage by body weight.</p>
No potential conflict of interest relevant to this article was reported.Okayama University Medical SchoolActa Medica Okayama0386-300X4941995Effects of exposure to cigarette smoke on intestinal propulsion in rats.201204ENKatsushiFurunoMasatoshiOkazakiKoheiEtoHiromuKawasakiYutakaGomitaArticle10.18926/AMO/30377<p>The effects of acute exposure to cigarette smoke and systemic administration of nicotine on intestinal propulsion were investigated in rats. The propulsive activity was measured as migration of charcoal powder in the intestine. This activity was suppressed by acute exposure (10 min) to cigarette smoke and by nicotine (0.5 mg/kg x 2, s.c.) administration. This intestinal suppression was more marked in the rats given nicotine than in those exposed to cigarette smoke, whereas the plasma concentrations of nicotine in both rats were similar. These results suggest that acute exposure to cigarette smoke and nicotine administration delay gastric emptying and/or suppress intestinal propulsion, and that some components other than nicotine contained in cigarette smoke may attenuate the suppression of intestinal propulsion induced by nicotine.</p>
No potential conflict of interest relevant to this article was reported.岡山実験動物研究会Acta Medica Okayama232006脊髄穿刺ラットを用いた循環薬理学的研究3335ENShingoTakatoriHiromuKawasakiMitsunobuMioNo potential conflict of interest relevant to this article was reported.