Search PubMed⌕ Search

Biomedical subjects

Y Kiuchi

Publications and source records attributed to Y Kiuchi.

At least 19 recordsLinked to original sources
PubMed1995

Effects of various dopamine uptake inhibitors on striatal extracellular dopamine levels and behaviours in rats.

In vivo central effects of some dopamine uptake inhibitors were evaluated in both brain microdialysis and behavioural studies in rats, and compared with their in vitro affinities to dopamine uptake sites. IC50 values of GBR12909 (1-[2- bis(4-fluorophenyl)methoxy]ethyl]-4-(3- phenylpropyl)piperazine), diclofensine, mazindol, amfonelic acid and nomifensine for inhibiting 1 nM [3H]GBR12935 (1-[2-(diphenylmethoxy)ethyl]-4-(3-phenylpropyl)piperazine) binding to rat striatal membrane were 7.0, 36, 81, 187 and 290 nM, respectively. In the brain microdialysis study, dopamine levels in the striatal dialysates were increased to 16.3- (GBR12909), 14.1- (nomifensine), 4.8- (diclofensine) and 1.9-fold (amfonelic acid) the respective basal levels 40-60 min after i.p. administration (0.1 mmol/kg) and thereafter decreased slowly but remained at the elevated levels for a further 3 h, while mazindol gradually increased dopamine levels though less pronouncedly than others (1.7-fold 200 min after administration). Remarkable and comparable stereotyped behaviours (licking and forepaw treading) were continuously observed at least for 3 h after administration of GBR12909, nomifensine and amfonelic acid, while stereotypies induced by diclofensine and mazindol were moderate and marginal, respectively. In vivo potencies of dopamine uptake inhibitors to increase the extracellular dopamine levels in the striatum tended to correlate with their in vitro affinities to dopamine uptake sites except in the case of nomifensine, and correlated significantly with their potencies to induce stereotyped behaviours except in the case of amfonelic acid. Based on these findings, pharmacological characteristics of these dopamine uptake inhibitors are discussed.

Animals↗
PubMed1995

Augmented production of tumor necrosis factor-alpha in obese mice.

Non-insulin-dependent diabetes mellitus develops in obesity. The insulin resistance of this disease may be mediated by tumor necrosis factor-alpha (TNF-alpha). In particular, the TNF-alpha derived from adipose tissues might be involved in the induction of peripheral insulin resistance in rodent models of obesity. In general, monocytes/macrophages have been considered as the major source of TNF-alpha. This study was designed to examine the potential production of TNF-alpha from monocyte/macrophages in obese mice. In obese (ob/ob) and obese diabetic (db/db) mice, both of which are known to have severe insulin resistance, unstimulated serum bioactivity of TNF-alpha was significantly higher than that in lean control mice. Spontaneous TNF-alpha mRNA expression in splenic macrophages was also enhanced in obese mice, but not in monosodium-L-glutamate (MST)-induced obese mice which have no insulin resistance. In addition, both ob/ob and db/db mice produce more TNF-alpha than lean mice upon in vivo lipopolysaccharide (LPS) stimulation. The LPS-induced increase in serum TNF-alpha activity was not observed in MSG-induced obese mice. Taken together, it is postulated that TNF-alpha produced by monocytes/macrophages may also play an important role in the genesis of insulin resistance in obesity. Further study is needed to reveal the mechanism of enhanced TNF-alpha production in obese states and its possible etiologic relevance to obesity.

Animals↗
PubMed1995

Ca(2+)-dependent enhancement of [3H]dopamine uptake in rat striatum: possible involvement of calmodulin-dependent kinases.

We studied effects of Ca2+ in the incubation medium on [3H]dopamine ([3H]DA) uptake by rat striatal synaptosomes. Both the duration of the preincubation period with Ca2+ (0-30 min) and Ca2+ concentration (0-10 mM) in Krebs-Ringer medium affected [3H]DA uptake by the synaptosomes. The increase was maximal at a concentration of 1 mM Ca2+ after a 10-min preincubation (2.4 times larger than the uptake measured without preincubation), which reflected an increase in Vmax of the [3H]DA uptake process. On the other hand, [3H]DA uptake decreased rapidly after addition of ionomycin in the presence of 1 mM Ca2+. The Ca(2+)-dependent enhancement of the uptake was still maintained after washing synaptosomes with Ca(2+)-free medium following preincubation with 1 mM Ca2+. Protein kinase C inhibitors did not affect apparently Ca(2+)-dependent enhancement of the uptake, whereas 1(-)[N,O-bis(1,5-isoquinolinesulfonyl)-N-methyl-L- tyrosyl]-4-phenylpiperazine (KN-62; a Ca2+/calmodulin-dependent kinase II inhibitor) and wortmannin (a myosin light chain kinase inhibitor) significantly reduced it. Inhibitory effects of KN-62 and wortmannin appeared to be additive. N-(6-Aminohexyl)-5-chloro-1-naphthalenesulfonamide hydrochloride (W-7; a calmodulin antagonist) also remarkably inhibited the enhancement. These results suggest that Ca(2+)-dependent enhancement of [3H]DA uptake is mediated by activation of calmodulin-dependent protein kinases.

Animals↗
PubMed1995

Wistar fatty rat is obese and spontaneously hypertensive.

The purpose of this study was to determine whether genetically obese Wistar fatty rats have higher blood pressure than their lean littermates and if so to elucidate the mechanism of this obesity-related hypertension. We measured blood glucose and plasma insulin levels, blood pressure, and catecholamine and sodium excretions in age-matched female Wistar fatty and lean rats. After 12 weeks of age, the body weight of Wistar fatty rats was significantly greater than that of their lean counterparts. Fasting blood glucose and plasma insulin concentrations were higher in the fatty than the lean rats throughout the observation period (8 to 24 weeks of age). Systolic blood pressure of fatty rats measured by the tail-cuff method was similar to that of lean rats at 8 weeks of age (135 +/- 2 [mean +/- SEM] versus 134 +/- 3 mm Hg) but significantly higher at 16 (158 +/- 2 versus 136 +/- 3 mm Hg, P < .01) and 24 (166 +/- 5 versus 142 +/- 2 mm Hg, P < .01) weeks of age. Urinary norepinephrine excretion was significantly increased in the fatty rats at both 16 (1755 +/- 173 versus 977 +/- 128 ng/24 h, P < .05) and 24 (1907 +/- 283 versus 737 +/- 173 ng/24 h, P < .01) weeks of age. The ratio of urinary norepinephrine excretion to body weight was also significantly increased in the fatty rats. These results show that with increasing body weight Wistar fatty rats develop hypertension, which may be attributable to an increased sympathetic nerve activity.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1995

Deodorization of laboratory animal facilities by ozone.

Deodorizing effect of ozone was investigated comparing two types of compact ozonizing apparatus made on an experimental basis. The concentrations of ammonia and trimethylamine were examined as an indicator for deodorizing effect of ozone in animal rooms of rats and guinea pigs at laboratory animal facilities of three different universities. Both of the ozonizing apparatus were able to remove ammonia and trimethylamine in animal rooms, with no significant difference in the performance of the two apparatus.

Ammonia↗
PubMed1995

Light exposure decreases IOP in rabbits during the night.

Elevated IOP observed in rabbits during the dark phase of the circadian cycle decreased rapidly and reversibly when rabbits were exposed to light during the dark phase. The decrease of IOP does not result from decreased aqueous flow and only part of the decrease requires intact ocular sympathetic innervation.

Animals↗
PubMed1995

Pharmacokinetic study of trimethadione and its metabolite in blood, liver and brain by microdialysis in conscious, unrestrained rats.

A microdialysis method has been developed in the past two decades to determine levels of drug and endogenous compounds in several organs under physiological conditions. In this study, we determined the pharmacokinetics of the model drug, trimethadione (TMO), and its only metabolite, dimethadione (DMO), in liver, blood and brain by the microdialysis method in freely-moving rats. Sampling times were extended up to 24 hours. The construction of a newly developed microdialysis probe for liver and blood is described. The elimination patterns of TMO in liver, blood and brain dialyzates were almost identical and the calculated t1/2 was approximately 3 hr in each sample. However, in brain, tmax was delayed compared with the others while the relative concentration of DMO (AUC0-24h) was lower in brain compared with liver and blood. These studies suggest that this concurrent and successive microdialysis sampling method will not only be a useful tool for pharmacokinetic and drug metabolism studies in the organs of small animals but will also decrease the number of experimental animals needed for a study.

Animals↗
PubMed1995

[Increase in extracellular levels of serotonin and amino acids in the rat brain following cyanide-induced energy failure].

We studied the effects of ATP depletion on neurotransmitter release in the rat brain using the microdialysis method. Ringer's solution containing 2 mM sodium cyanide (NaCN) was perfused into the hippocampus and striatum for 60 min via a microdialysis probe, and changes in serotonin (5-HT) and amino acids (glutamate, aspartate and taurine) levels in dialysates were investigated. NaCN perfusion induced a transient 3.9-fold increase in 5-HT levels in the hippocampal dialysate. Amino acid levels in dialysates also increased during NaCN perfusion, but differently in the striatum and hippocampus (glutamate: 1.3- and 2.4-fold, taurine: 2.3- and 1.3-fold, respectively). Perfusion of Ca(2+)-free Ringer's solution remarkably suppressed the NaCN-induced increase in 5-HT but not the increases in amino acid levels. Depolarization by 100 mM KCl perfusion could induce increases in 5-HT and amino acids in dialysates at 3 hr after NaCN perfusion similarly with that of control. These findings indicate that the sensitivity of nerve terminals to energy failure are different between neurons containing different neurotransmitters and also between brain regions, and suggest that this regionally different sensitivity of amino acid neurons might be involved in the underlying mechanism of the localized vulnerability to transient ischemia.

Adenosine Triphosphate↗
PubMed1995

[Central ocular hypotensive effect of noradrenaline].

We investigated the effects of topical and central administration of noradrenaline (NA) on the intraocular pressure (IOP) in pigmented rabbits. Unilateral instillation of NA (200 micrograms) produced no significant change in IOP. On the other hand, intracerebroventricular (ICV) administration of NA (0.01-1 micrograms) decreased IOP in both eyes in a dose-related fashion. The ocular hypotensive effect of NA was diminished by sympathectomy of the superior cervical sympathetic nerve or by ICV pretreatment with yohimbine hydrochloride 1-10 micrograms). These results suggest that the hypotensive effects of contrally administered NA might be mediated by alpha 2-adrenoceptor stimulation in the central nervous system.

Administration, Topical↗
PubMed1994

Exercise intensity determines the magnitude of IOP decrease after running.

The effects of the intensity, duration and quantity (intensity x duration) of exercise on the reduction of intraocular pressure (IOP) in healthy and physically fit individuals were studied. Five minutes after 15 minutes of exercise at 70%, 55% and 40% of maximum exercise load (%HRmax) the IOP decreased 4.3 +/- 0.7 mmHg, 2.2 +/- 0.7 mmHg and 0.6 +/- 0.5 mmHg, respectively. The magnitude of IOP reduction increased with exercise load. Running for 7.5 minutes at 70%HRmax decreased IOP comparable to 15 minutes of running at the same exercise load (4.4 +/- 0.6 mmHg). Twenty-five minutes of running at 40%HRmax is almost the same quantity of exercise as 15 minutes of running at 70%HRmax. However, the former did not result in IOP reductions to equal the latter (2.3 +/- 0.5 vs 4.4 +/- 0.6 mmHg). The amount of IOP reduction after short-term exercise seems to depend on the intensity of exercise, not on the duration of exercise or the quantity of exercise.

Adult↗
PubMed1994

[Antidepressant and antimanic drugs--pharmacological mechanisms and pharmacokinetics].

In Japan, fifteen drugs, including tricyclic and non-tricyclic antidepressants or an MAO inhibitor, are clinically available for treatment of depression. However, the pharmacological mechanism(s) of their antidepressive effect remain uncertain. "Receptor hypothesis" that functional changes of monoamine receptors after chronic treatment, such as down-regulation of beta-adrenoceptor or 5-HT2 receptor, bring about a therapeutic effect, seems to be unsatisfactory. Recent studies focus on interaction between antidepressants and intracellular signal transduction pathways. For effective and safe uses of antidepressants, especially in aged patients or those with hepatic and renal diseases, pharmacokinetics such as distribution, protein binding and metabolism must be well understood. In this paper, pharmacokinetic characteristics of antidepressants are also reviewed.

Antidepressive Agents↗
PubMed1993

Role of calcium ions in dopamine release induced by sodium cyanide perfusion in rat striatum.

We have previously reported a transient and remarkable increase in dopamine (DA) release in the rat striatum during application of 2 mM sodium cyanide (NaCN) through a brain microdialysis membrane. In the present study we examined the involvement of extracellular Ca2+ in this response. Rats were divided into 4 groups. In the NaCN group a microdialysis probe inserted into the striatum was perfused with Ringer's solution containing 2 mM NaCN for 60 min. The Ca2+ free + NaCN group was subjected to perfusion with NaCN dissolved in Ca2+ free Ringer's solution, and the CdCl2 + NaCN group with the same plus 0.3 mM CdCl2 (a non-specific Ca2+ channel blocker). In the NaCN and Ca2+ free + NaCN groups DA levels in the dialysates increased to 36- and 44-fold of the control level, respectively, while this was suppressed to only a 16-fold increase in the CdCl2 + NaCN group. In response to a 100 mM KCl perfusion given 3 hr later DA levels were increased (22-fold) in the control group. On the other hand this response was inhibited in the NaCN group (3-fold), but not in the other two groups. An in vitro study with striatal slices showed a gradual increase in intracellular Ca2+ during incubation with 2 mM NaCN. These results suggest that excessive influx of extracellular Ca2+ during NaCN perfusion may contribute partly to the increase in the extracellular DA level in the striatum, and also to the suppression of a DA increase in response to high K+ stimulation observed 3 hr later.

Animals↗
PubMed1993

Sustained increase in adrenergic activity in gerbil striatum following transient ischemia.

We investigated the changes in striatal monoaminergic functions, focusing on the release and metabolism, in a cerebral ischemic model induced by a 5-min bilateral occlusion of the carotid arteries (BOCA) and reperfusion in anesthetized gerbils. In the microdialysis study, the striatal extracellular level of dopamine (DA) markedly increased (144-fold) immediately after BOCA. Although norepinephrine (NE) and 5-hydroxytryptamine (5-HT) could not be detected in the dialysates throughout the baseline period, they increased to detectable levels after BOCA. On the contrary, the tissue contents of NE and 5-HT decreased or tended to decrease up to 4 hr following reperfusion. Striatal DA contents did not show any changes in the early period after ischemia-reperfusion and slightly increased at 4 hr or later. Tissue contents of 3-methoxytyramine (3-MT), a metabolite of DA by catechol-O-methyltransferase (COMT), increased 0 and 5 min after reperfusion. Normethanephrine (NMN), which is a metabolite of NE by COMT, also increased not only 5 min after but also up to 4 hr after ischemia-reperfusion, indicating a sustained increase in NE release. These results suggested that the neuronal activity of NE, which is supposed to exert a protective effect on ischemic damage, was enhanced for a longer period than that of DA after transient ischemia.

Animals↗
PubMed1993

Effects of the contents of dietary crude protein on growth rate and NK activity.

The relationship between body weight gain and food intake was examined using 3 strains of mice, C3H/He, C57BL/6 and A/J mice, that were fed 4 kinds of diets differing in crude protein contents. Body weight gain of the mice fed the diet containing 3% protein was extremely small, while that of the mice fed the diet containing 40% protein was smaller than that of the mice fed the diet containing 10% or 20% protein. Mice were shown to possess a characteristic ability to intake an almost constant amount of calories irrespective of crude protein contents in diets, with some exceptions. These experimental results indicate that crude protein intake plays an important role for body weight gain. It was also assumed that energy consumption in C57BL/6 mice fed the 40% protein diet was accelerated because of excessive protein intake. Normal NK activity and antibody responses to SRBC were maintained at the age of 12 weeks in all the strains of mice fed the different diets.

Animal Nutritional Physiological Phenomena↗
PubMed1993

Melatonin does not increase IOP significantly in rabbits.

New Zealand white rabbits have a circadian rhythm of intraocular pressure; pressure is higher during the dark than during the light. We explored the possibility that the dark phase increase of serum and/or ocular melatonin plays a role in regulating the rhythm of intraocular pressure. Exogenous melatonin was delivered by four routes: topical application (0.1 and 10 micrograms), intravenous injection (1 microgram), intravitreal injection (9 micrograms) and intra-arterial infusion (50 ng and 1 microgram). Melatonin delivered by these routes did not increase intraocular pressure. We also measured the concentration of melatonin in the aqueous after unilateral intra-arterial infusion to confirm that melatonin delivered by this route reached the eye. The concentration was 419 +/- 99 and 109 +/- 17 pg/ml (n = 8, p < 0.025) in the ipsilateral and contralateral eyes, respectively. The concentration of melatonin in the aqueous after intra-arterial infusion of saline was less than the sensitivity of the assay (< 16 pg/ml, n = 6). The results of these experiments indicate that melatonin does not increase IOP significantly under the experimental conditions employed in this study.

Administration, Topical↗
PubMed1993

Binding of antiglaucomatous drugs to synthetic melanin and their hypotensive effects on pigmented and nonpigmented rabbit eyes.

The binding of ocular hypotensive drugs to synthetic melanin was studied spectrophotometrically in vitro. The ocular hypotensive effects of the drugs, namely, timolol, befunolol, carteolol, pilocarpine, epinephrine, prostaglandin A2, F2 alpha and E2, also were compared in vivo on eyes of pigmented and albino rabbits. At an initial concentration of 10(-4) M, each of the three beta-blockers exhibited a binding rate of 80-85% as compared to only 40% for pilocarpine and 50% for epinephrine. Almost none of the prostaglandins were found to bind to synthetic melanin. Topically applied, 0.5% timolol and 3% pilocarpine significantly lowered the intraocular pressure in albino but not in pigmented rabbits. Epinephrine (1%) caused a significant reduction in the intraocular pressure both in albino and pigmented rabbits; however, the maximum reduction was greater in albino than in pigmented rabbits. Intraocular pressure was reduced to the same extent and with a similar time-course in both albino and pigmented rabbits by 0.02% prostaglandin A2, F2 alpha and E2. These findings show that several ocular hypotensive drugs bind to melanin and suggest that this process can modify the extent of their pharmacological effects when tested in a single dose, or the time-course of their effects when used to treat chronic conditions.

Adrenergic beta-Antagonists↗
PubMed1993

Ophthalmic diseases in bedridden patients with severe dementia.

Ophthalmologic examinations were performed on the 176 eyes of 88 bedridden patients with severe dementia. There were some pathologic changes in the external and anterior segments of 93 eyes. We observed infectious external and anterior segment eye diseases in 80 of these 93 eyes (86.0%). Fundus diseases were found in 34 eyes, but treatment was not necessary. Infectious eye diseases appeared to be the most prevalent ocular problem in these patients. Cultures of conjunctival swabs commonly demonstrated Staphylococcus aureus. No differences were noted in tear secretion rate or lysozyme concentrations in tears between eyes with and without infection. The blinking frequency was significantly reduced in infected eyes compared to normal eyes. Failure of the lacrimal drainage system was observed more often in infected eyes than in normal eyes. This study demonstrated that bedridden patients with severe dementia develop infectious eye diseases easily, to which stasis of tear flow seems to predispose. In caring for bedridden patients with severe dementia, ophthalmologists must be concerned with controlling infectious eye diseases.

Adult↗