Biomedical subjects

Y Gomita

Publications and source records attributed to Y Gomita.

At least 19 recordsLinked to original sources

PubMed1999

Determination of plasma phenobarbital concentration by high-performance liquid chromatography in rat offspring.

Plasma phenobarbital (PB) concentrations in rat offspring were determined using a 9 microl capillary by high-performance liquid chromatography (HPLC). Capillary plasma which was put into a Bond Elut cartridge column by using 1 ml of 0.01 M KH2PO4 was applied to the column with 50 microl of 2 microg/ml of acetanilide (internal standard, I.S.). After washing the column, PB and I.S. were eluted with methanol and injected into the HPLC system. There were excellent linear correlation between the amount of PB and length of the capillary at three different concentrations. Calibration for PB was linear in the range of 0-50 microg/ml. The coefficients of variation were 3.4-5.0% and 5.9-7.5% in the within-day and between-day assays, respectively. The extraction recovery rates were 87.5-105.4%. By this method, it was possible to measure plasma PB concentrations in rat offspring without killing. These results suggested that this method is very useful to determine the plasma PB concentration derived from mother's milk in newborn rats.

Animals↗

PubMed1999

Effect of dopamine blockers on cerebral ischemia-induced hyperactivity in gerbils.

When common carotid arteries of Mongolian gerbils were clamped for 5 min, locomotor activity significantly increased the day after the ischemic insult. This hyperactivity induced by cerebral ischemia was evident in both light and dark periods. The significant increases in locomotor activity seen in both periods were noted for 3 and 9 days after occlusion, respectively. Effects of dopamine receptor antagonists on the ischemia-induced hyperactivity were investigated the day after the ischemia insult. Haloperidol, sulpiride, and eticlopride, all dopamine D2 receptor antagonists, decreased the ischemia-induced hyperactivity at doses that had no effects on locomotor activity in sham-operated animals. SCH23390, a dopamine D1 receptor antagonist, had no clear effects on the ischemia-induced hyperactivity. Clozapine, with not so high an affinity for the dopamine D2 receptor decreased the ischemia-induced hyperactivity when given in a relatively high dose. Thus, the ischemia-induced hyperactivity is apparently related to abnormalities in dopaminergic functions, particularly the dopamine D2 receptor.

Animals↗

PubMed1999

Effect of calcium channel blockers on cerebral ischemia-induced hyperactivity in Mongolian gerbils.

When both common carotid arteries of Mongolian gerbils were occluded for 5 min to produce ischemic insult, locomotor activity was increased the following day. The effect of calcium channel blockers on this ischemia-induced hyperactivity was investigated. Nimodipine, at doses of 5, 10, and 20 mg/kg, dose dependently and significantly decreased ischemia-induced hyperactivity. Nicardipine significantly decreased ischemia-induced hyperactivity and doses of 10 and 20 mg/kg. Nifedipine and flunaridine also significantly decreased ischemia-induced hyperactivity at doses of 20 mg/kg. Verapamil had no effect on ischemia-induced hyperactivity at a dose of 20 mg/kg. These findings suggest that ischemia-induced hyperactivity is related to calcium channels. These relationship between calcium channels and dopaminergic function is discussed.

Animals↗

PubMed1999

Long-term treatment with angiotensin converting enzyme inhibitor restores reduced calcitonin gene-related peptide-containing vasodilator nerve function in mesenteric artery of spontaneously hypertensive rats.

Effects of long-term treatment with angiotensin converting enzyme (ACE) inhibitor on decreased function of calcitonin gene-related peptide (CGRP)-containing vasodilator nerves (CGRP nerves) in mesenteric resistance artery were investigated in spontaneously hypertensive rats (SHR). Eight-week-old SHR were treated for 7 weeks with 0.1% captopril, 0.01% temocapril, 0.05% pindolol or 0.005% hydralazine in drinking water. Long-term treatment with each drug significantly lowered mean blood pressure of SHR. In isolated and perfused mesenteric vascular beds with active tone, periarterial nerve stimulation (PNS) (0.5 to 8 Hz) produced frequency-dependent vasodilations, which were abolished by CGRP(8-37) (CGRP-receptor antagonist) and significantly smaller in SHR than in normotensive Wistar Kyoto rats. Treatment of SHR with captopril and temocapril but not with pindolol and hydralazine resulted in significantly greater PNS-induced vasodilation than in non-treated SHR, but ACE-inhibitor treatment did not affect vasodilation induced by exogenous CGRP. In captopril-treated SHR preparations, PNS evoked significantly larger CGRP-like immunoreactive release than in non-treated SHR. In non-treated 15-week-old SHR preparations, direct perfusion of captopril or temocapril (0.1 microM and 1 microM) did not modify frequency-dependent vasodilation in response to PNS. These results suggest that long-term ACE inhibitor treatment prevents or restores CGRP nerve function reduction in SHR.

Angiotensin-Converting Enzyme Inhibitors↗

PubMed1999

The effects of exposure to cigarette smoke on the pharmacokinetics and pharmacodynamics of zonisamide in rats.

The effects of exposure to cigarette smoke on the pharmacokinetics and pharmacodynamics of zonisamide, an antiepileptic drug, were investigated in rats. Absorption of oral zonisamide was significantly inhibited by exposure to cigarette smoke. The Cmax, T1/2 and the area under the plasma concentration-time curve 0-24 values in the cigarette smoke exposure group were significantly lower than those in the control group. Although tonic extension (TE) induced by maximal electroshock was completely blocked by the administration of zonisamide in the control group, 50% of rats showed TE in the cigarette smoke exposure group. Exposure to cigarette smoke influences both the pharmacokinetics and antiepileptic effects of zonisamide. The effects of smoking on epileptic patients using zonisamide warrants further attention.

Animals↗

PubMed1998

Inhibition of neuronal dopamine uptake by some antiallergic drugs.

The effects of 10 antiallergic drugs (astemizole, azelastine, ebastine, emedastine, epinastine, ketotifen, oxatomide, terfenadine, pemirolast and tranilast) on neuronal dopamine uptake were examined. Some drugs examined showed a concentration-dependent inhibition of [3H]dopamine uptake into synaptosomal preparations of the rat striatum. The inhibition constant (Ki) values were 231-876 nM for ebastine, terfenadine, oxatomide and astemizole. The specific binding of [3H] (1-[2-(diphenylmethoxy)ethyl]-4-(3-phenylpropyl)piperazine) (GBR12935) to the rat striatal membranes was also inhibited by these antiallergic drugs. There was a good correlation between the degrees of inhibition of [3H]dopamine uptake and [3H]GBR12935 binding. Then, the behavioral excitement induced by L-DOPA (100 mg/kg, s.c.) plus pargyline hydrochloride (80 mg/kg, i.p.) in mice was significantly enhanced by i.p. treatment with ebastine (10 mg/kg) and astemizole (5 mg/kg). These results suggest that the neuronal dopamine uptake is inhibited by some antiallergic drugs, especially ebastine.

Animals↗

PubMed1998

Age-related decrease in centrally-mediated pressor response to clonidine in conscious rats.

An age-related change in pressor response to intracerebroventricular (i.c.v.) injection of clonidine in conscious rats was investigated. In 15-week-old rats, clonidine (2 to 20 micrograms) caused a dose-dependent pressor response concomitant with decrease in heart rate. The depressor response to i.c.v. clonidine at lower doses (2 and 5 micrograms) but not higher doses (10 and 20 micrograms) was observed. The pressor response to clonidine in 20- and 30-week-old rats was markedly diminished, and the depressor response appeared at any of the doses injected. However, no age-related change in heart rate responses was observed. These results suggest that the centrally mediated pressor response to clonidine is age-related and masks the depressor response.

Adrenergic alpha-Agonists↗

PubMed1998

Involvement of calcitonin gene-related peptide (CGRP) receptors in insulin-induced vasodilatation in mesenteric resistance blood vessels of rats.

1. The vascular effect of insulin in the mesenteric resistance blood vessel and the role of calcitonin generelated peptide (CGRP)-receptor in insulin-induced vascular responsiveness were investigated in rats. 2. The mesenteric vascular beds isolated from Wistar rats were perfused with Krebs solution, and perfusion pressure was measured with a pressure transducer. In preparations contracted by perfusion with Krebs solution containing methoxamine in the presence of guanethidine, the perfusion of insulin (from 0.1 to 3000 nM) caused a concentration-dependent decrease in perfusion pressure due to vasodilatation. The pD2 value and maximum relaxation (%) were 6.94+/-0.22 and 43.9+/-5.2, respectively. 3. This vasodilator response to insulin was unaffected by 100 nM propranolol (beta-adrenoceptor antagonist) plus 100 nM atropine (muscarinic cholinoceptor antagonist), 100 microM L-NG-nitroarginine (nitric oxide synthase inhibitor), 1 microM ouabain (Na+-K+ ATPase inhibitor), or 1 microM glibenclamide (ATP sensitive K+-channel inhibitor). 4. In preparations without endothelium, perfusion of insulin produced a marked vasodilatation. The pD2 value and maximum relaxation (%) were 7.62+/-0.21 and 81.0+/-4.6, respectively, significantly greater than in preparations with intact endothelium. 5. The vasodilator responses to insulin in the preparations without endothelium were significantly inhibited by CGRP[8 37], a CGRP receptor antagonist, whereas pretreatment with capsaisin, a toxin for CGRP-containing nerves, did not affect insulin-induced vasodilatation. 6. These results suggest that insulin induces non-adrenergic, non-cholinergic and endothelium-independent vasodilatation, which is partially mediated by CGRP receptors.

Animals↗

PubMed1998

Steady-state serum concentrations of carbamazepine and valproic acid in obese and lean patients with epilepsy.

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.

Adolescent↗

PubMed1998

Repeated mazindol and methamphetamine administration produces cross-sensitization to stereotyped behavior induced by these agents in rats.

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.

Animals↗

PubMed1998

Involvement of the central catecholaminergic system in nicotine-induced tail-tremor in rats.

The effect of 6-hydroxydopamine on repeated nicotine-induced tail-tremor was investigated in rats. Tail-tremor induced by nicotine (0.5 mg/kg/day, subcutaneously) became more pronounced in intensity with daily administration for 9 days. Rats pretreated with 6-hydroxydopamine (250 micrograms, intracerebroventricularly) showed almost the maximum degree of tail-tremor during the whole experimental period. However, in rats pretreated with 6-hydroxydopamine plus desipramine, enhancement of tail-tremor was slight in the beginning but increased with the daily nicotine administration. Fourteen-day administration of nicotine did not result in significant changes in noradrenaline and dopamine levels in the cortex, hypothalamus, striatum and nucleus accumbens. These results suggest that nicotine-induced tail-tremor is associated with the supersensitivity of postsynaptic catecholaminergic receptors in the central nervous system, and that the noradrenergic system may be more important than the dopaminergic system in this phenomenon.

Animals↗

PubMed1998

Angiotensin inhibits neurotransmission of calcitonin gene-related peptide-containing vasodilator nerves in mesenteric artery of spontaneously hypertensive rats.

The role of angiotensin (Ang) in neurotransmission of calcitonin gene-related peptide (CGRP)-containing vasodilator nerves in perfused mesenteric vascular beds isolated from spontaneously hypertensive rats (SHR) (8- and 15-week-old) and age-matched Wistar Kyoto rats (WKY) was investigated. In both SHR and WKY preparations precontracted by continuous perfusion of Krebs' solution containing 7 microM methoxamine plus 5 microM guanethidine, periarterial nerve stimulation (PNS; 1 and 2 Hz) produced a frequency-dependent vasodilation, which was abolished by 100 nM tetrodotoxin and 500 nM CGRP(8-37) (CGRP receptor antagonist). The PNS-induced vasodilation in the SHR decreased with age and was smaller than that in the WKY. The neurogenic vasodilation in the SHR but not WKY was significantly inhibited by N-acetyltetradecapeptide renin substrate (RS, 100 and 500 nM), AngI (50 and 100 nM) and AngII (50 and 100 nM). The inhibitory effects of RS, AngI and AngII were abolished by the AngII receptor antagonist, [Sar1,Ile8]AngII (500 nM). The effect of RS and AngI was inhibited by captopril (5 microM) and temocapril (500 nM). AngII (100 nM) had no effect on vasodilator response to exogenously infused CGRP (100 pmol). PNS (2 Hz) of perfused mesenteric vascular beds increased the release of CGRP-like immunoreactivities (CGRP-LI) in the perfusate, which was less in 15-week-old SHR than in age-matched WKY. AngII (100 nM) significantly inhibited the neurogenic release of CGRP-LI in the SHR but not in the WKY. These results suggest that exogenous and locally converted AngII, via AngII receptors, modulates the neurotransmission of CGRP-containing vasodilator nerves by inhibiting CGRP release from the nerve.

Angiotensin I↗

PubMed1997

Involvement of nitric oxide in development of tail-tremor induced by repeated nicotine administration in rats.

Daily administration of nicotine (0.5 mg/kg per day s.c.) to rats caused a tremor that appeared only in the tail (tail-tremor) and which became more marked over 8 days. Nitric oxide (NO) synthase inhibitors, Nw-nitro-L-arginine (10 mg/kg per day i.p.) or Nw-nitro-L-arginine methyl ester (20 and 40 mg/kg per day i.p.), administered each day before nicotine attenuated the development of the tail-tremor. However, neither Nw-nitro-L-arginine (2-10 mg/kg i.p.) nor Nw-nitro-L-arginine methyl ester (10-40 mg/kg i.p.) affected the tail-tremor that developed after 14 days of repeated nicotine administration. The noncompetitive N-methyl-D-aspartate (NMDA) receptor antagonist, MK-801 ((+)-5-methyl-10,11,-dihydro-5H-dibenzo[a,b]cyclohepten-5,10-imine hydrogen maleate) at 0.2 mg/kg per day (i.p.), or competitive antagonist, CPP (3-[(+/-)-2-carboxypiperazin-4-yl] propyl-1-phosphonic acid) at 2 mg/kg per day (i.p.), administered each day before nicotine attenuated the development of the tail-tremor. MK-801 (0.01-0.2 mg/kg i.p.) but not CPP (0.5-4 mg/kg i.p.) suppressed the tail-tremor that developed after 14 days of repeated nicotine administration. These results suggest that NO formation mediated by NMDA receptors is involved in the mechanisms underlying the tail-tremor induced by the repeated administration of nicotine.

Animals↗

PubMed1997

Role of central nicotinic and beta-adrenergic receptors in the onset and further development of tail-tremor induced by repeated nicotine administration to rats.

The effects of nicotinic and beta-adrenergic receptor antagonists on tail-tremor induced by repeated nicotine administration were investigated in rats. The daily administration of nicotine (0.5 mg/kg/day, s.c.) for 8 days resulted in an augmentation of tail-tremor. However, repeated administration of dimethyl phenyl piperazinium iodide (1 mg/kg/day, s.c.) for 8 days did not cause tail-tremor. Mecamylamine (0.5 mg/kg, i.p), administered before the nicotine injection on each day, abolished the tail-tremor. After discontinuation of the mecamylamine treatment, nicotine injections caused tail-tremor augmentation. Propranolol (20 mg/kg, i.p.), administered before the nicotine on each day, suppressed the appearance of tail-tremor. After the discontinuation of propranolol treatment, the degree of tail-tremor induced by a single injection of nicotine on day 9 was much greater in the propranolol-treated group than in the saline-treated control group. Neither carteolol (20 mg/kg, i.p.) nor metoprolol (20 mg/kg, i.p.) treatment showed such effects. Intraspinal injection of 6-hydroxydopamine markedly enhanced the tail-tremor induced on the first day of nicotine injection. This effect became more intense on subsequent administration of nicotine. The enhanced tail-tremor following 6-hydroxydopamine treatment was abolished by mecamylamine (0.5 and 1 mg/kg, i.p.), and was suppressed by propranolol (5-20 mg/kg, s.c.) in a dose-dependent manner. These results suggest that central nicotinic receptors are essential for the onset and for the further development of tail-tremor induced by the repeated administration of nicotine, and that beta 2-adrenoceptors are associated with the tremor mechanism. Moreover, spinal noradrenergic mechanisms may be involved in the manifestation of this phenomenon.

Adrenergic Agents↗

PubMed1997

Effects of dopaminergic agents on reversal of reserpine-induced impairment in conditioned avoidance response in rats.

Male Slc:Wistar, Std:Wistar, and Slc:F344/N rats had good acquisition of the conditioned avoidance response (CAR), while that of the male Slc:Wistar/ST, Jcl:Wistar, and Crj:Wistar rats was bad. Reserpine-induced impairment (RII) in CAR was observed 2-72 h after administration of dopaminergic (DAergic) agents in male Slc:Wistar rats. Amitriptyline (5-80 mg/kg, P.O.), imipramine, desipramine, cis-dosulepine, and trans-dosulepine at dose of 40 mg/kg, P.O. showed no antagonism against RII in CAR 20-23 h after reserpine injection (1 mg/kg, S.C.). However, the atypical antidepressive agents sibutramine (5-10 mg/kg, P.O.), bupropion (40 mg/kg, P.O.), and nomifensine (10-40 mg/kg, P.O.) exhibited antagonism against RII in CAR. The calcium channel antagonists flunarizine, nimodipine, and KP-840 at dose of 10 and 100 mg/kg, P.O., the cerebral improving agent indeloxazine (20-80 mg/kg, P.O.), the anticholinergic agent atropine (5-40 mg/kg, P.O.), 5-hydroxy-L-tryptophan (5-HTP) (40 mg/kg, I.P.), a precursor of 5-hydroxytryptamine (5-HT), and (+/-)-threo-dihydroxyphenylserine [(+/-)-threo-DOPS] (20-200 mg/kg P.O.), a norepinephrine (NE) precursor, showed no antagonism against RII in CAR. The DAergic agents methamphetamine (5 mg/kg, P.O.) and amantadine (50-250 mg/kg, P.O.), L-DOPA (200 mg/kg, P.O.), and the DAergic D1/D2 receptor agonist apomorphine (0.1-1 mg/kg, S.C.) showed marked antagonism against RII in CAR. Although the DAergic D1-receptor agonist KF-38393 (0.3-30 mg/kg, I.P.) and the DAergic D2-receptor agonist quinpirole (0.3-10 mg/kg, I.P.) induced only a weak recovery of RII in CAR when they were administered alone, in contrast to a potent synergistic recovery of RII in CAR, which was observed when SKF-38393 (1 mg/kg, I.P.) and quinpirole (1 mg/kg, I.P.) were administered together. These results suggest that the DAergic nervous system rather than the adrenergic or 5-HT nervous system is involved in RII in CAR, and that both the DAergic D1- and D2-mediated nervous systems play important roles in this process.

Animals↗

PubMed1997

Potentiometric flow injection determination of serum bromide in patients with epilepsy.

A flow injection system was constructed using a bromide-selective electrode and used to determine serum bromide in patients with epilepsy. A 10-microliter serum sample was injected into a carrier stream flowing at 0.12 ml min-1. Potential changes and bromide concentrations were linearly related in the range 3-50 mM. The lower limit of detection for serum bromide was 1 mM and this electrode sensitivity spanned the entire concentration range required for bromide therapy (9-24 mM). The results compared favourably with those obtained by colorimetry.

Autoanalysis↗

PubMed1997

Effects of various antiepileptic drugs on plasma levels of lamotrigine, a novel antiepileptic, in rats.

The pharmacokinetics of lamotrigine (LTG) and effects of carbamazepine (CBZ), valproic acid (VPA) and zonisamide (ZNS) on LTG kinetics were investigated in rats. LTG plasma levels were measured by high-performance liquid chromatography (HPLC). A single oral administration of LTG at 2.5-10 mg/kg showed linear disposition kinetics. In the pharmacokinetic parameters of LTG when combined with CBZ, the maximal plasma concentration (Cmax) and the area under the plasma concentration curve (AUC0-36) values were significantly lower and the time to maximal plasma concentration (Tmax) value was significantly higher than those in LTG alone. Furthermore, the Cmax and AUC0-36 values of LTG when pretreated with CBZ for 7 days were significantly lower than those from simultaneous treatment with CBZ. The Cmax and AUC0-36 values of LTG when combined with VPA were significantly lower than those for LTG alone. There was no significant difference in the Tmax or time of elimination half-life (t1/2) values of LTG between simultaneous and pretreatment with VPA. Of the pharmacokinetic parameters of LTG with ZNS combination, the Cmax value of LTG after long-term dosings of ZNS decreased significantly, whereas no significant change in Cmax was observed after the combined single administration of LTG and ZNS. Single and chronic ZNS treatment did not significantly affect the Tmax, t1/2 and AUC0-36 values of LTG. The LTG trough level was significantly reduced by CBZ administration, reached the bottom level at 6 days after starting CBZ administration, and recovered gradually after withdrawal of CBZ. These results suggest that CBZ, VPA and ZNS causes changes in the plasma LTG level. They also suggest that in therapy combining LTG with one of these antiepileptics, especially CBZ, the LTG concentration in plasma should be monitored carefully.

Administration, Oral↗

PubMed1997

Influence of lactation on plasma phenobarbital concentrations in rats.

The effect of lactation on the pharmacokinetics of phenobarbital (PB) after delivery was studied in female rats. Non-pregnant animals received PB 20 mg/kg/day twice for 6-7 days before mating, during pregnancy and after delivery. Chronic PB did not significantly influence changes in the body weight of rats after delivery. On the first post-delivery day, the plasma PB concentration in the PB-treated rats was significantly higher than that in PB-treated, non-pregnant rats (non-pregnant rats); and thereafter, it gradually decreased until ablactation on the 20th day. After ablactation, plasma PB concentrations gradually returned to the level before delivery. In PB-treated rats, pharmacokinetic parameters (Cmax, AUC0-12) of PB between 0 and 12 hr after a single oral administration were significantly decreased during lactation. These results suggest that PB administered during lactation is transferred in part to offspring through maternal milk.

Administration, Oral↗