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Biomedical subjects

N Ozaki

Publications and source records attributed to N Ozaki.

At least 19 recordsLinked to original sources

[The effects of centrifugal pump on liver support system with porcine liver perfusion].

The effects of vaneless centrifugal pump (Bio-pump P-80) on energy metabolism were studied, as compared with the roller pump, in an isolated porcine liver perfused with human blood for 6 hours. According to preliminary examination, flow rates were decided to 0.4, 0.8 ml/min/g in roller pump group, in Bio-pump pump group, respectively, not to increase more than 15 mmHg in initial portal pressure. During the perfusion, actual portal pressure was measured and circulatory resistance (portal pressure/flow rate) was calculated before perfusion and hourly after perfusion. Acetoacetate, beta-hydroxybutyrate, lactate and pyruvate, were measured at same times, from which values the ketone body ratio (acetoacetate/beta-hydroxybutyrate, KBR), reflecting the redox state of liver mitochondria, was calculated. In the Bio-pump group, in spite of its high flow, circulatory resistance was low at every hour during the perfusion. KBR was increased rapidly from 0.40 to 1.39, 2.59, 2.75, 2.38, 2.41, and 1.82 and lactate was decreased rapidly from 7.96 to 3.90, 1.77, 1.29, 1.33, 1.34, and 1.25 mmol/L at the respective hours after perfusion. There were significant differences at 2 and 4 hours after perfusion in KBR and after 2 hours of perfusion in lactate as compared with the roller pump group (p < 0.05). These results suggested that the Bio-pump is available for constant and high flow to the liver and helpful to elevate the mitochondrial NAD/NADH ratio (oxidized and reduced forms of free nicotinamide-adenine dinucleotides), leading to and enhancement of metabolic capacity of the perfused liver.

Adult

Differential effect of self-stimulation on dopamine release and metabolism in the rat medial frontal cortex, nucleus accumbens and striatum studied by in vivo microdialysis.

Changes in the extracellular levels of dopamine (DA) and its metabolites in the dopaminergic terminal regions, the medial frontal cortex (MFC), nucleus accumbens (NAC), and striatum (STR), were measured by microdialysis during self-stimulation of the medial forebrain bundle (MFB) in rats pretreated with the DA uptake inhibitor, nomifensine (1 mg/kg, i.p.). Self-stimulation of the MFB in nomifensine-pretreated rats caused an increase in the extracellular DA level in the MFC and NAC but not in the STR. Self-stimulation also increased the extracellular concentrations of the main DA metabolites, 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) to a similar extent in the MFC and NAC and to a lesser extent in the STR. Thus, there was a regional difference in the neurochemical changes following self-stimulation with either the MFC or the NAC showing larger extracellular levels of DA, DOPAC, and HVA than the STR. Furthermore, these changes were observed on both hemispheres ipsilateral and contralateral to the stimulation. The results indicate that self-stimulation of the MFB preferentially activates the mesocorticolimbic DA systems, thereby bilateral increases in the release of DA and its metabolism being produced in their terminal regions, the MFC and NAC.

3,4-Dihydroxyphenylacetic Acid

Receiver operating characteristic (ROC) analysis of the ability of arterial ketone body ratio to predict graft outcome after liver transplantation--its sensitivity and specificity.

To evaluate the ability of arterial ketone body ratio (AKBR; acetoacetate/3-hydroxybutyrate) to predict graft prognosis after liver transplantation, the diagnostic value as a predictive index was compared between AKBR and conventional liver function tests using receiver operating characteristic (ROC) analysis. The ROC curves were determined for AKBR, GOT, GPT, total bilirubin, serum lactate level, and prothrombin time, all of which were measured on the 1st and 2nd postoperative days in 88 cases of liver transplantation. Comparisons of the areas under the ROC curves between AKBR and other tests revealed the significant superiority of AKBR to other tests in predicting graft death within 1 month after transplantation. The present study suggests that AKBR can be used as an accurate index to predict graft prognosis after liver transplantation.

Adolescent

Mechanism of prostaglandin E2-induced arachidonic acid release in osteoblast-like cells: independence from phosphoinositide hydrolysis.

We previously reported that pertussis toxin (PTX)-sensitive GTP-binding protein is involved in the coupling of prostaglandin E2 (PGE2) receptor to phospholipase C in osteoblast-like MC3T3-E1 cells (1). In the present study, we analyzed the mechanism of PGE2-induced arachidonic acid (AA) release in MC3T3-E1 cells. PGE2 stimulated the release of AA and the formation of inositol trisphosphate (IP3) dose dependently in the range between 1 nM and 10 microM. The effect of PGE2 on AA release (ED50 was 80 nM) was more potent than that on IP3 formation (ED50 was 0.8 microM). Quinacrine, a phospholipase A2 inhibitor, suppressed the PGE2-induced AA release but had little effect on the IP3 formation. NaF, a GTP-binding protein activator, mimicked PGE2 by stimulating the AA release. The AA release stimulated by a combination of PGE2 and NaF was not additive. PTX had little effect on the PGE2-induced AA release. These results strongly suggest that the AA release and the phosphoinositide hydrolysis are separately stimulated by PGE2 in osteoblast-like cells, and the PGE2-induced AA release is mediated by PTX-insensitive GTP-binding protein.

Arachidonic Acid

The effect of methamphetamine on serotonin and its metabolite in the suprachiasmatic nucleus: a microdialysis study.

The suprachiasmatic nucleus (SCN) has been identified as a major circadian pacemaker. Methamphetamine has been shown to modify the behavior of circadian rhythms. We detected extracellular serotonin (5-HT) and its metabolite 5-hydroxyindoleacetic acid (5-HIAA) in the SCN in freely moving rats, using a microdialysis method, to investigate biochemical effects of methamphetamine in the SCN. Methamphetamine infusion into the SCN dose-dependently increased extracellular 5-HT and decreased extracellular 5-HIAA.

Animals

Electrical characteristics in an excitable element of lipid membrane.

Electrical characteristics in a membrane constructed from a porous filter adsorbed with a lipid analogue, dioleoyl phosphate (DOPH), were investigated in a situation interposed between 100 mM NaCl + 3 mM CaCl2 and 100 mM KCl. Calcium ions affected significantly the membrane characteristics. The membrane potential was negative on the KCl side, which implies the higher permeability to K+ than Na+; this tendency was increased by a tiny amount of Ca2+. While the membrane showed a low electrical resistance of several k omega . cm2 under K+/Na+ gradient, it showed several M omega . cm2 by Ca2+. The surface structure of the membrane exhibited many voids in the low-resistance state, but the surface was covered by oil droplets in the high-resistance state. Oscillations of the membrane potential appeared spontaneously with application of the electrical current from the KCl side to the NaCl + CaCl2 side. The frequency was increased with the electrical current. All these results were explained comprehensively using an electrochemical kinetic model taking account of the Ca2+ binding effect, where DOPH assemblies make a phase transition between oil droplets due to Ca2+ and multi-bilayers with excess K+. The oscillation arises from coupling of the phase transition to accumulation and release of K+ or Ca2+. This membrane can be used as an excitable element regulated by Ca2+ in neuro-computer devices.

Calcium

Sexual difference and organ specificity of the effect of estradiol on carbonic anhydrase and Mg(2+)-HCO3(-)-ATPase activities isolated from duodenal mucosa and kidney cortex of male and female rats: preliminary study with crude enzyme samples.

Effects of the s.c. administration of various doses of estradiol propionate (E.P.; 25-500 micrograms/kg) on the activities of carbonic anhydrase (CA), Mg(2+)-dependent ATPase and Mg(2+)-dependent, HCO3(-)-stimulated ATPase (Mg(2+)-HCO3(-)-ATPase) in rat duodenal mucosa and kidney cortex, and on body weight, organ weight and serum concentrations of testosterone and estradiol-17 beta, were examined in adult male, female, testectomized and ovariectomized rats. In normal male rats, activities of cytosol CA and brush border Mg(2+)-HCO3(-)-ATPase in the kidney were increased in a dose-dependent manner and reached 1.6- and 2-fold of controls, respectively, after consecutive administration (daily for 7 days) of 500 micrograms E.P. with no changes in either enzyme activities in duodenal mucosa. The positive correlations (P less than 0.01) were observed by linear regression analysis between serum concentration of estradiol-17 beta and kidney cytosol CA or kidney brush border Mg(2+)-HCO3(-)-ATPase activities. In normal female rats, activities of cytosol CA and brush border Mg(2+)-HCO3(-)-ATPase in the duodenal mucosa, and brush border Mg(2+)-HCO3(-)-ATPase activity in the kidney were increased by E.P. administration (100 and 500 micrograms/kg, daily for 7 days), however, kidney cytosol CA activity did not change by any dosage. Behavior of a part of both enzymes to E.P. in testectomized rats was altered almost in the same way to that observed in normal female rats and vice versa in ovariectomized rats. Body weight was decreased, in general, by consecutive administration of E.P. in a dose-dependent manner, and kidney weight was increased by E.P. in both male and female rats.

Animals

[Methodological considerations in microdialysis].

Microdialysis has rapidly become popular in recent years as an in vivo technique to monitor endogenous substances in the extracellular space of the local brain region. The combination of this technique with a variety of highly sensitive detection methods has enabled us to measure in vivo release of various neurotransmitters. However, the technique involves several methodological problems. The first is that the concentrations of substances in the dialysate only partially reflect their true concentrations in the extracellular space. Therefore, neurotransmitters such as neuropeptides that are present at very low concentrations in the extracellular space are still difficult to detect. The second problem is the effects of tissue damage by the microdialysis probe. Though the probe has been miniaturized, severe disturbance in tissue metabolism cannot be neglected. Histological examination suggests that the most suitable time for commencing microdialysis is between 24 and 48 h after probe implantation. The third problem is that neurotransmitters recovered in the dialysate are sometimes not involved in neurotransmission. It is suggested that the dialysate concentration of a neurotransmitter which reflects neuronal activity should be both tetrodotoxin-sensitive and calcium-dependent. In the case of a neurotransmitter in the dialysate which does not show these characteristics, its concentration may be related to metabolic rather than neurogenic events. The fourth problem is that microdialysis has poor time resolution. Therefore, the method is not suitable for measurement of neurochemical events that rapidly change in short intervals such as milliseconds or seconds. Thus careful consideration has to be given to these problems in the actual laboratory use of microdialysis technique.

Animals

Treatment of persistent sleep-wake schedule disorders in adolescents with methylcobalamin (vitamin B12).

Two adolescent patients suffering from persistent sleep-wake schedule disorders appear to have responded to treatment with vitamin B12 (methylcobalamin). A 15-year-old girl with delayed sleep phase syndrome (DSPS) and a 17-year-old boy with hypernychthemeral syndrome complained of not being able to attend school despite many trials of medication. The improvement of the sleep-wake rhythm disorders appeared immediately after the administration of high doses (3,000 micrograms/day) of methylcobalamin. Neither patient showed any laboratory or clinical evidence of vitamin B12 deficiency or hypothyroidism (which can cause B12 deficiency). Serum concentrations of vitamin B12 during treatment were in the high range of normal or above normal. The duration of the sleep period of the DSPS patient decreased gradually from 10 hours to 7 hours, and the time of sleep onset advanced from 2 a.m. to midnight. The period of the sleep-wake cycle of the hypernychthemeral patient was 24.6 hours before treatment and 24.0 hours after treatment. The relationship between the circadian basis of these disorders and vitamin B12 and its metabolites is discussed.

Achievement

Involvement of pertussis toxin-sensitive GTP-binding protein in prostaglandin F2 alpha- induced phosphoinositide hydrolysis in osteoblast-like cells.

Prostaglandin F2 alpha (PGF2 alpha) stimulated the formation of inositol phosphates in a dose-dependent manner in cloned osteoblast-like MC3T3-E1 cells. This reaction was markedly inhibited dose-dependently by pertussis toxin. In the cell membranes, pertussis toxin-catalyzed ADP-ribosylation of a 40-kDa protein was significantly attenuated by pretreatment of PGF2 alpha. These results suggest that pertussis toxin-sensitive GTP-binding protein is involved in the coupling of PGF2 alpha receptor to phospholipase C in these cells.

Animals

[Microdialysis: a method to construct a microdialysis probe and its applications].

This paper describes a removable microdialysis probe constructed inexpensively and easily from a commercially available iv catheter placement unit and flexible fused silica tubing. The probe is characterized in in vitro recovery tests. As an example of its applications, experimental results measuring extracellular dopamine concentrations in the nucleus accumbens of rats during intracranial self-stimulation behavior are reported.

Animals

Reduced arterial ketone body ratio during laparotomy: an evaluation of operative stress through the changes in hepatic mitochondrial redox potential.

The present article discusses the evaluation of surgical stress on the basis of the hepatic functional capacity of each patient. The changes in arterial blood ketone body ratio (KBR; acetoacetate/beta-hydroxybutyrate), which reflects hepatic mitochondrial redox potential, following intraoperative procedures were investigated in 60 laparotomy cases, including 30 cases with partial hepatectomy. The time course of changes in KBR was obtained by serial measurement during operation. The total area below the KBR level of 0.7 was defined as the hepatic stress score (HSS). HSS was significantly greater in the cases with hepatectomy (43.5 +/- 9.1; mean +/- SE) than in others (16.5 +/- 4.2; p less than 0.01). HSS in 13 patients accompanied by postoperative complications (60.4 +/- 17.7) was also significantly greater than that in the patients with uneventful postoperative courses (22.1 +/- 4.3; p less than 0.05). The former was also accompanied by significantly larger postoperative catabolic response preceding the clinical onset of complications (p less than 0.001). In the cases with uneventful postoperative courses, analysis of variance revealed that nitrogen balance and catabolic index in the first postoperative week were dependent on HSS negatively and positively, respectively (p less than 0.005), indicating a causative relationship between the suppression of hepatic energy metabolism during operation and the enhanced postoperative catabolic response. These results suggest that total surgical stress in major laparotomy can be quantitated and evaluated through the magnitude of decrease in hepatic mitochondrial redox potential, and that this evaluation may provide valuable information for intraoperative and postoperative patient care.

3-Hydroxybutyric Acid

The effect of uptake inhibition on dopamine release from the nucleus accumbens of rats during self- or forced stimulation of the medial forebrain bundle: a microdialysis study.

Changes in dopamine (DA) release were measured in microdialysis samples taken from the nucleus accumbens (NAC) of rats pretreated with the DA uptake inhibitor, nomifensine (1 mg/kg, i.p.) during self- or forced stimulation of the medial forebrain bundle (MFB). Self-stimulation of the MFB in nomifensine-pretreated rats caused an increased release of DA in the NAC. In the same rats, similar increases in DA release were also found during forced stimulation, that is, during MFB stimulation in the absence of lever-pressing, but at current and rate parameters identical to those recorded in the previous self-stimulation session. The results indicate that self-stimulation of the MFB activates the mesolimbic DA system; similar neurochemical changes observed during self- and forced stimulation of the MFB suggest that the operant lever-pressing behavior itself did not influence DA release in the NAC.

Animals

Increased dopamine and serotonin metabolism in rat nucleus accumbens produced by intracranial self-stimulation of medial forebrain bundle as measured by in vivo microdialysis.

In the present study, we have used a newly developed microdialysis system to perfuse the nucleus accumbens (NAC) of conscious rats during spontaneous intracranial self-stimulation of the medial forebrain bundle (MFB). Chromatographic (HPLC-ECD) analysis of the perfusates showed that dopamine (DA) release increased, but with an unstable pattern during the actual period of self-stimulation. On the other hand, the main DA metabolites, 3,4-dihydroxyphenylacetic acid and homovanillic acid, and a serotonin metabolite 5-hydroxyindoleacetic acid, were all markedly enhanced by self-stimulation, but with different time courses. These findings indicate that self-stimulation of the MFB in rats induces increases in both DA and serotonin activities in the NAC. Such changes may be involved in mediating self-stimulation of the MFB.

3,4-Dihydroxyphenylacetic Acid

Influence of hypoxia on mitochondrial function and energy status in CCl4-induced cirrhotic rat liver.

The influence of hypoxia on hepatic mitochondrial function and energy status was studied in normal and carbon tetrachloride (CCl4)-induced cirrhotic rats. Under hypoxemia of 50 mm Hg-PaO2, hepatic energy status was suppressed both in normal and cirrhotic rats. After the reversal of hypoxia, it was completely restored in normal rats concomitant with a rapid elevation of hepatic mitochondrial redox state (overshoot phenomenon) and increase in the mitochondrial oxidative phosphorylative activity. By contrast, in cirrhotic rats, such an enhancement of mitochondrial function was not observed. It was clarified that cirrhotic liver mitochondrial function was not observed. It was clarified that cirrhotic liver mitochondria have little capacity to respond to the hypoxic stress. A lower resistance to hypoxic episode in cirrhotics might be attributable to the absence of mitochondrial enhancement which is a compensatory mechanism for the deranged energy metabolism of the liver.

Animals