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Biomedical subjects

T Okutomi

Publications and source records attributed to T Okutomi.

At least 37 records · Page 2Linked to original sources
PubMed1996

Cooperative anti-Candida effects of lactoferrin or its peptides in combination with azole antifungal agents.

The effects of lactoferrin (LF), an antimicrobial protein secreted in body fluids, and its peptides in combination with azole antifungal agents were investigated by the micro-broth-dilution method in a study of Candida albicans. In the case of LF, its pepsin hydrolysate (LFhyd) or the LF-derived antimicrobial peptide Lactoferricin B (LF-B), the concentrations required to inhibit the growth of Candida decreased in the presence of relatively low concentrations of clotrimazole (CTZ). The minimum inhibitory concentration (MIC) of all azole antifungal agents tested was reduced by 1/4-1/16 in the presence of a sub-MIC level of each of these LF-related substances. Polyene and fluoropyrimidine antifungal agents did not show such a combined effect with these LF-related substances. The anti-Candida activity of LF or LF-B in combination with CTZ was shown to be synergistic by checkerboard analysis. These results indicate that LF-related substances function cooperatively with azole antifungal agents against C. albicans.

Antifungal Agents↗
PubMed1995

Autogenous production of hydroxyl radicals from thiopental.

It is generally believed that barbiturates can protect neural tissues from the damage induced by cerebral hypoxia. One of the mechanisms for protecting neurons is through the inhibition of lipid peroxidation (LPO). We therefore examined LPO in rat brain, liver and kidney by measuring the accumulation of thiobarbituric acid-reactive substances (TBAR) after thiopental administration under 21% O2. We also designed an in vitro study to gain insight into free radical generation leading to the formation of LPO from thiopental by electron spin resonance (ESR). An accumulation of TBAR in the rat liver was observed after the administration of a large dose of thiopental (70 mg/kg intraperitoneally). However, no change in LPO in the brain and kidney was observed. In the in vitro study, thiopental could scavenge superoxide (O2-.) radicals, while it spontaneously generated hydroxyl radicals (.OH) in solution. We conclude that thiopental can scavenge O2-., while producing .OH, subsequently resulting in membrane lipid peroxidation under physiologic O2 conditions. This formation of .OH may damage cell membrane lipids.

Animals↗
PubMed1995

[Immunomodulator as medicine for morphine and cocaine dependence. Especially effect of LPS].

The majority of medicines developed for narcotic and stimulant dependence were agonists or antagonists of neurotransmitters and their receptors. Recently it has been shown that the nervous system, the endocrine system and the immune system are regulated by mutual interaction. The nervous system and the endocrine system are influenced by an immunomodulator, and the immune system is regulated by a neurotransmitter. In this report, medicines for morphine and cocaine dependence are first surveyed and then medicines for drug dependence through the activation of the immune system are introduced including our results which show the effect of macrophage activator such as LPS on morphine and cocaine dependence. The LPS purified from Pantoea agglomerans showed a relief effect on physical dependence of morphine and psychic dependence of cocaine, while it induced endogenous opioid, beta-endorphin. The induction of beta-endorphin was recognized to be in synchrony with the time course and dose response of the relief of dependence. These data suggest the participation of endogenous opioid such as beta-endorphin induced by LPS after the activation of macrophage leading to the relief of morphine and cocaine dependence.

Adjuvants, Immunologic↗
PubMed1995

[Pharmacokinetics of balofloxacin in the intraocular tissues of pigmented rabbits].

We performed the pharmacokinetics of balofloxacin in plasma and intraocular tissues in pigmented rabbits upon its oral administration. The penetrations of balofloxacin into plasma and aqueous humor of the anterior chamber reached their peaks of 6.46 micrograms/ml and 0.70 microgram/ml, respectively, and the ratio of drug concentration in aqueous humor to that of plasma was 0.12 at 1 hour after an oral administration of 20 mg/kg. Concentrations in plasma and aqueous humor of the anterior chamber reached 0.27 microgram/ml and 0.18 microgram/ml, respectively, at The T 1/2 (alpha) and T 1/2 (beta) of the drug in aqueous humor were longer than those in plasma The T 1/2 (alpha) and T 1/2 (beta) of the drug in aqueous humor were longer than those in plasma at a dose of 20 mg/kg. The concentrations in iris and ciliary body were much higher than in any other intraocular tissue in 24 hours after single administration of 20 mg/kg, and those concentrations remained at high levels for a long time.

Administration, Oral↗
PubMed1995

Pharmacokinetics of the new fluoroquinolone balofloxacin in mice, rats, and dogs.

The pharmacokinetics of 1-cyclopropyl-6-fluoro-1, 4-dihydro-8-methoxy-7-(3-methylaminopiperidin-1-yl)-4-oxoquinoline -3-carboxylic acid dihydrate (CAS 127294-70-6, balofloxacin, Q-35), a new fluoroquinolone, were studied in mice, rats and dogs by high performance liquid chromatography. The mean oral bioavailabilities of balofloxacin calculated from the area under the curve after oral and intravenous administration in mice, rats and dogs were 19.03, 87.50 and 87.73%, respectively, indicating that balofloxacin was almost completely absorbed in rats and dogs but not in mice after single oral administration. The mean elimination half-lives in plasma after intravenous administration in mice, rats and dogs were 0.92, 1.33 and 6.38 h, respectively. Mean cumulative urinary excretion percentages of unchanged balofloxacin within 24 h of oral administration of balofloxacin at the dose of 20 mg/kg in mice, rats and dogs were 4.91, 21.77 and 22.49% of the dose, respectively. A small portion of the metabolite was excreted into urine as balofloxacin glucuronide and N-desmethyl balofloxacin in these species. After oral administration of balofloxacin at the dose of 100 mg/kg to rats, absorption was prolonged compared with that after administration at the doses of 5 and 20 mg/kg. Plasma concentration-time profiles and pharmacokinetic parameters of balofloxacin in male rats were similar to those in female rats, indicating no sex-related differences. Once daily 21-day multiple administrations had not affect on these pharmacokinetic profiles of balofloxacin in rats.

Administration, Oral↗
PubMed1994

Antinociceptive effect of lipopolysaccharide from Pantoea agglomerans on streptozotocin-induced diabetic mice.

The antinociceptive effect of lipopolysaccharide from Pantoea agglomerans (LPSp) in streptozotocin-induced diabetic mice was examined. Although subcutaneous (s.c.) administration of LPSp produced a dose-dependent inhibition of the tail-flick response in both non-diabetic and diabetic mice, the antinociceptive response was greater in diabetic mice than in non-diabetic mice. The antinociceptive effects of LPSp in both diabetic and non-diabetic mice were significantly antagonized by s.c. administration of naltrindole, a selective delta-opioid receptor antagonist or nor-binaltorphimine, a selective kappa-opioid receptor antagonist, but not by beta-funaltrexamine, a selective mu-opioid receptor antagonist. These results suggest that LPSp produces a marked antinociceptive effect in diabetic mice through the activation of delta- and kappa-opioid receptors.

Analgesics↗
PubMed1994

Effects of a lipopolysaccharide from Pantoea agglomerans on the cocaine-induced place preference.

A lipopolysaccharide from Pantoea agglomerans (LPSp) was purified, and its effect on the cocaine-induced place preference was examined in rats. Cocaine (4 mg/kg, i.p.) produced a significant place preference. Administration of LPSp (5-1000 micrograms/kg, i.p.) alone resulted in neither preference nor aversion for either the drug- or saline-associated place. However, pretreatment with LPSp (500 and 1000 micrograms/kg, i.p.) abolished the place preference that had been induced by cocaine. Furthermore, treatment with LPSp (500 micrograms/kg, i.p.) abolished cocaine (20 mg/kg, i.p.)-induced locomotor enhancement in mice. These results suggest that while LPSp itself may possess neither reinforcing nor locomotor enhancing effects, it blocks both the reinforcing and the locomotor enhancing effects of cocaine. Therefore, LPSp might be useful in pharmacotherapy for prevention of recurrent cocaine abuse.

Animals↗
PubMed1994

Suppression of hyperalgesia in streptozotocin-induced diabetic mice by a lipopolysaccharide from Pantoea agglomerans.

The ability of a lipopolysaccharide from Pantoea agglomerans (LPSp) to relieve hyperalgesia was examined by observing its inhibition of the decrease in the threshold for nociceptive perception, as determined by the tail-pinch test, in streptozotocin-induced diabetic mice. Subcutaneous injection of LPSp suppressed hyperalgesia in streptozotocin-induced diabetic mice and also exerted a therapeutic effect on hyperalgesia in these animals. The present data suggest that LPSp may be effective in relieving the pain associated with diabetic neuropathy.

Animals↗
PubMed1993

Time course in thoracic epidural pressure measurement.

The purpose of this study was to measure thoracic epidural pressure at the time of insertion of an epidural needle. The pressure was measured using a closed pressure measurement system after insertion of a Tuohy needle at the T7-8 intervertebral level. This system is unique because it has a pressure transducer equipped with a device which regulates flow through the transducer and prevents the heparinized saline in the system from being evacuated into the epidural space due to sudden pressure change. As reported previously, high negative epidural pressures, up to -60 mmHg, were observed at the moment of epidural puncture. However, the pressure became positive in about 30 sec in 12 of the 13 patients, and stabilized at +3.7 +/- 3.2 mmHg (mean +/- SD) within 90 sec. Similar results were observed when the procedure was repeated within a few minutes to the same patients. This suggests that negative epidural pressures at the moment of epidural puncture are artifacts induced by tenting of the dural membrane. Subsequent adaptation of the surrounding tissue results in restoration of the normal positive epidural pressure.

Adaptation, Physiological↗
PubMed1993

[The sprotte needle decreases the incidence of postspinal headache].

Postspinal headache (PSH) is the most frequent complication of spinal anesthesia. The factors responsible for the development of PSH include needle size, shape of the needle tip, patient's age, sex, infusion volume and period of resting. The purpose of this study is to compare the incidence of PSH between two different types of needle, Sprotte needle and Quincke needle. The Sprotte needle is characterized by a round profiled tip equipped with a lateral orifice. Our investigation by questionnaires revealed that the incidences of PSH after using either 22G Sprotte needle or 21-25G Quincke needle were 0% and 38.8%, respectively. We conclude that the Sprotte needle decrease the incidence of PSH.

Adult↗
PubMed1992

Homeostasis as regulated by activated macrophage. IV. Analgesic effect of LPSw, a lipopolysaccharide of wheat flour.

The effect of LPSw, a lipopolysaccharide from a water extract of wheat flour, on pain response was investigated using an acetic acid-induced writhing test in mice. LPSw inhibited writhing dose-dependently in the range of 10 ng-10 micrograms/mouse i.v. This effect reached its maximum 1.5-3 h after the LPSw inoculation and was detectable even after 8 h. The analgesic effect of LPSw was inhibited by i.v. injection of naloxone and also beta-endorphin was detected in serum and brain tissue following injection of LPSw. Preliminary clinical trials were done in which LPSw was administered percutaneously to relieve the pain of patients with herpes. The results showed that pain was relieved by this application. LPSw may be the best analgesic drug so far known, since it induces the endogenous mediator of analgesia, beta-endorphin.

Analgesics↗
PubMed1992

Homeostasis as regulated by activated macrophage. V. Suppression of diabetes mellitus in non-obese diabetic mice by LPSw (a lipopolysaccharide from wheat flour).

A lipopolysaccharide from wheat flour (LPSw) which was isolated and characterized is shown to exert definitely a suppressive effect on incidence of type 1 diabetes in mice. Therapeutic effect on type 2 diabetes in patients was also obtained, though only from preliminary results. The percutaneous route of administration is most favorable. The important role that precursor tumor necrosis factor, free or cell bound, may play in this mechanism is discussed.

Animals↗
PubMed1992

Homeostasis as regulated by activated macrophage. VII. Suppression of serum cholesterol level by LPSw (a lipopolysaccharide from wheat flour) in WHHL (Watanabe heritable hyperlipidemic) rabbit.

The effect of LPSw (a lipopolysaccharide from wheat flour) on cholesterol catabolism was examined using WHHL (Watanabe heritable hyperlipidemic) rabbit, which is an experimental model of familial hyperlipidemia. The serum cholesterol level of the animal decreased by the addition of LPSw to drinking water. Following cessation of the addition of LPSw to the drinking water, the cholesterol level was decreased for 30 to 40d and then gradually elevated. The serum level of apolipoprotein B, which is a constituent of apolipoprotein of low density lipoprotein (LDL), also decreased in accord with serum cholesterol at a nearly coincident rate. Conversely, the level of apolipoprotein A-I, which is a constituent of apolipoprotein of high density lipoprotein (HDL), did not change, nor did HDL-cholesterol. Furthermore, the atherosclerosis risk factor, expressed as the ratio of apolipoprotein B to apolipoprotein A-I, was decreased by LPSw administration.

Animals↗
PubMed1992

Homeostasis as regulated by activated macrophage. VIII. LPSw (a lipopolysaccharide from wheat flour) can regulate bone resorption of chick embryo.

The effect of LPSw (a lipopolysaccharide from wheat flour) on the bone resorption of 18-d chick embryonic calvaria was examined in an organ culture following the method of Raisz. Bone was prelabeled in culture medium containing 45Ca and chased in a cold medium. On addition of test samples, labeled calcium was released indicating the grade of bone resorption. LPSw (10-100 ng/ml) stimulated bone resorption, showing an effect comparable to parathyroid hormone (PTH) (1 U/ml). PTH at 1 U/ml decreased the total amount of calcium and phosphorus, while LPSw did not. LPSw is thus assumed to stimulate bone resorption more actively than PTH.

Animals↗
PubMed1992

Homeostasis as regulated by activated macrophage. IX. Enhancement effect of LPSw (a lipopolysaccharide from wheat flour) on hen egg-laying and breaking strength of eggshell.

Oral administration of LPSw (a lipopolysaccharide from wheat flour) given at 60 micrograms/hen/d in drinking water, markedly enhanced eggshell strength. The monthly percentage of eggs laid with a shell strength of more than 4 kg to the total number of eggs was 32% in the group given LPSw in drinking water while it was 12% in the control group given plain water. At the same time, LPSw caused a 30% enhancement of total monthly number of eggs laid over that of control.

Animals↗
PubMed1992

Homeostasis as regulated by activated macrophage. I. Lipopolysaccharide (LPS) from wheat flour: isolation, purification and some biological activities.

Based on our new concept of ontogenic inflammation, we have sought a substance which can prime macrophage in terms of the endogenous production of tumor necrosis factor (TNF). A lipopolysaccharide (LPSw) was found in wheat flour, purified and characterized. The molecular size of LPSw was about 5 kDa on sodium dodecyl sulfate-polyacrylamide gel electrophoresis, and it contained 3-deoxy-D-manno-octulosonic acid: 1, hexosamine: 4 and one phosphorus in a single molecule. LPSw can prime macrophage to release TNF when given intradermally, percutaneously or even orally in mice as well as in humans, in exactly the same way as intravenous administration of interferon gamma.

Administration, Oral↗