Biomedical subjects

T Inubushi

Publications and source records attributed to T Inubushi.

At least 55 records · Page 3Linked to original sources

PubMed1997

Relationship between gluconeogenesis and phosphoenergetics in rat liver assessed by in vivo 13C and 31P NMR spectroscopy.

The relationship between the phosphoenergetic state and gluconeogenesis in the liver after ischemic damage was investigated using living rats. The ATP level was determined with in vivo 31P nuclear magnetic resonance spectroscopy, and gluconeogenesis was evaluated with in vivo 31C NMR spectroscopy using L-[3-13C]alanine as a tracer. These two measurements were alternated repeatedly. The rats were divided into three groups: without ischemia (group A); with 10 min ischemia (group B); and with 30 min ischemia (group C). ATP was depleted to 20% of the preischemic state after 10 min ischemia and this level was maintained during 30 min ischemia. After reperfusion, the ATP level was partially restored, but the recovery was smaller in group C. Infusion of [3-13C]alanine was started immediately after the reperfusion. In vivo 13C NMR disclosed changes in the alanine C3, glutamine/glutamate C2 and C3, glucose C1-6, and glycogen C1 signals in the liver. After 60 min infusion of [3-13C]alanine, the ATP level correlated negatively with the signal intensity of alanine (r = -0.664, p = 0.008) and positively with those of glucose and glyogen (r = 0.586, p = 0.023, and r = 0.643, p = 0.011, respectively). These results suggest that the ATP level participates in gluconeogenesis and glycogenesis in the liver. Such multinuclear in vivo NMR observations might uncover new aspects of the metabolic function of the liver in the in vivo state.

Adenosine Triphosphate↗

PubMed1997

Acute 3-nitropropionic acid intoxication induces striatal astrocytic cell death and dysfunction of the blood-brain barrier: involvement of dopamine toxicity.

Mechanisms underlying the selective vulnerability of the lateral striatal area to the toxic effects of 3-nitropropionic acid (3-NPA) were investigated in rats. A single exposure to 3-NPA (20 mg/kg, s.c.) induced no deficits in behavior and histology, but subsequent injection produced motor symptoms, catalepsy, lip smacking, abnormal gait, paddling, rolling, opisthotonos, tremor, recombence, somnolence and so on, in 30% of the animals within a few hours. Diffusion-weighted magnetic resonance imaging of the brains revealed an area of high signal intensity in the bilateral striata. By this stage (within a few hours), striatal astrocytes had become swollen and disintegrated. Extravasation of immunoglobulin G was detected, indicating blood-brain barrier (BBB) dysfunction. Electron microscopy revealed edema and disorganization of structures inside the astrocytic end-feet around the branches of the lateral striatal artery. Neurons were less vulnerable than astrocytes to the 3-NPA injury. Treatment of the rats with D2 receptor agonist prior to exposure to 3-NPA attenuated the behavioral abnormalities and histological damage whereas pretreatment with D2 antagonist exacerbated these changes. The concentrations of extracellular dopamine (DA) and dihydroxyphenyl acetic acid (DOPAC) were both increased in rats exposed to 3-NPA. In vitro imaging of astrocytes revealed a progressive increase in [Ca2+]i after superfusion with 3-NPA, and the 'ceiling' level was maintained even after extensive washing. DA superfusion also increased the astrocytic [Ca2+]i and this increase was reversible. Data indicate that 3-NPA-induced striatal damage was associated with astrocytic cell death and dysfunction of the BBB. Intracellular edema and extreme Ca2+ overload induced by the toxin were further aggravated by an increase in the level of DA activity. These factors acting either singly or in combination may trigger astrocyte destruction.

Animals↗

PubMed1997

Phosphorus-31 magnetic resonance spectroscopic observations in 4 cases with anorexia nervosa.

1. Brain phosphorus metabolism was examined using phosphorus-31 magnetic resonance spectroscopy in 4 patients with anorexia nervosa. 2. In 4 patients examined before treatment, phosphodiester (PDE) peak area was significantly higher than that in 13 normal females. 3. In 6 data points in 4 patients, lower levels of PME were associated with malnutrition reflected by endocrinological abnormalities. 4. These data suggest that severe malnutrition in patients with anorexia nervosa may result in abnormality in membrane phospholipid metabolism, which might be responsible for brain atrophy in anorexia nervosa.

Adult↗

PubMed1997

The effects of halothane and isoflurane on the phosphoenergetic state of the liver during hemorrhagic shock in rats: an in vivo 31P nuclear magnetic resonance spectroscopic study.

We studied the effects of halothane versus isoflurane on the phosphoenergetic state and intracellular pH (pHi) of the rat liver using in vivo 31P nuclear magnetic resonance (NMR) spectroscopy during and after hemorrhagic shock. Seventeen rats were anesthetized with 1 minimum alveolar anesthetic concentration of halothane or isoflurane. The mean arterial blood pressure was reduced to 40 mm Hg and maintained at this level for 45 min by withdrawing blood from the common carotid artery. The shed blood was then returned slowly. In vivo 31P NMR spectra were consecutively collected throughout the study. The phosphoenergetic state of the liver was evaluated from the changes in adenosine triphosphate (ATP) and inorganic phosphate (P(i)) levels. pHi was calculated from the chemical shifts of P(i) and alpha-ATP peaks. During hemorrhagic shock, beta-ATP decreased to 35% and 45%, and P(i) increased to 300% and 230% of their initial values in the halothane and isoflurane groups, respectively. Intracellular acidosis was more severe in the halothane group. The recoveries of beta-ATP and P(i) were better in the isoflurane group. Halothane showed a more detrimental effect than isoflurane on the hepatic phosphoenergetic level during and after hemorrhagic shock.

Acidosis↗

PubMed1997

[Technical aspect of clinical spectroscopic imaging and its recent development--hardware and software].

Today's technical status as well as future developments of clinical spectroscopic imaging were overviewed in terms of hardware and software aspects. For the hardware development, discussion was focused on superconducting magnet with high static fields, new probe designs and fast acquisition of spectroscopic imaging. Some of the technical limitation was also included. In software, pulse shape design for B1 insensitive excitation, selective signal detection utilizing homo- and hetero-nuclear coherence transfer, and post processing of acquired data were briefly discussed. Especially the processed data is important to extract chemical information for the metabolite which can be utilize in the clinical application. Some of the proposed methods were summarized for this.

Computers↗

PubMed1997

[Clinical efficacy of three-dimensional chemical shift imaging (3D-CSI)--a study of 3D-CSI in the human heart and its clinical perspectives for the future].

The main purpose of this study was to investigate whether in vivo 31P three-dimensional chemical shift imaging(3D-CSI) of the human heart could serve as a useful tool for evaluating myocardial metabolism. We performed slice-selective 3D-CSI employing nuclear magnetic resonance(NMR) imaging with slice selection in one dimension and phase encoding in two dimensions. 31P NMR images of phosphocreatine (PCr) and ATP were superimposed on a corresponding 1H image of the heart. Our study revealed that while accurate in vivo 31P 3D-CSI measurement of the human heart is difficult to achieve it is not impossible, although various additional techniques for improving signal to noise ratio are indicated.

Adenosine Triphosphate↗

PubMed1996

Proton magnetic resonance spectroscopy of the basal ganglia in patients with schizophrenia: a preliminary report.

To examine metabolic changes in the left basal ganglia in chronic schizophrenia, we performed proton magnetic resonance spectroscopy (1H-MRS) in 21 medicated schizophrenic patients and 21 gender and age-matched normal controls. Compared to the normal subjects, the schizophrenic patients showed a significantly increased level of choline containing compounds (Cho) (t = 2.60, p < 0.05) and ratio of Cho to N-acetylaspartate (NAA) (t = 2.46, p < 0.05) in the left basal ganglia. No significant correlation was observed between the 1H-MRS measurements in the left basal ganglia and clinical symptom scores as evaluated using the Brief Psychiatric Rating Scale (BPRS). The chlorpromazine equivalent neuroleptic dosage was positively correlated with the level of NAA (r = 0.38, p < 0.05) and negatively correlated with the Cho/NAA ratio (r = -0.34, p < 0.05). These findings suggest that these changes in metabolites in the left basal ganglia may reflect some of the functional and morphological abnormalities reported previously for the brain in schizophrenia.

Adolescent↗

PubMed1996

High-energy phosphate metabolism in the frontal lobes of patients with panic disorder detected by phase-encoded 31P-MRS.

Using phosphorus-31 magnetic resonance spectroscopy (31P-MRS), we analyzed the brain phosphorous metabolism in 18 patients with panic disorder (PD) and in 18 sex-, age-, and handedness-matched normal controls (NC). All patients were receiving ongoing drug treatments for PD. The evaluation of phosphorous metabolism in the whole frontal lobes revealed no significant differences between the patients and controls in 31P metabolite levels, although the PD patients showed slightly decreased inorganic phosphate (Pi) concentration of the frontal lobes. Moreover, we found a significant asymmetry (left > right) of phosphocreatine (PCr) concentration in the frontal lobes in the patients with PD, suggesting that abnormalities of phosphorous metabolism are present in the frontal lobes of PD patients. Two patients in whom a limited panic episode occurred during measurements showed frontal lobe intracellular pH higher than that in the other patients and that in the NC, suggesting respiratory gaseous alkalosis due to hyperventilation in the anxiety state. 31P-MRS has potential for application in the assessment of brain abnormalities and anxiety state, such as that accompanied by hyperventilation, in PD patients.

Adolescent↗

PubMed1996

Glucose and energy metabolism in rat liver after ischemic damage assessed by 13 C and 31 P NMR spectroscopy.

Glucose and energy metabolism in rat liver after ischemic damage was investigated by in vivo 31P NMR spectroscopy, 1H-detected 13C NMR spectroscopy, and in vitro 13C NMR spectroscopy using [1-13C]glucose as a tracer. Arterial ketone body ratio (AKBR; acetoacetate/beta-hydroxybutylate) and oxygen consumption of isolated mitochondria were also examined to evaluate hepatic function. The rats were divided into three groups: (A) without ischemia, (B) 10-min ischemia, and (C) 30-min ischemia. ATP was almost depleted at 10 min of ischemia and recovered after reperfusion, but the recovery was not complete. The recovery after 30-min ischemia was smaller than that after 10-min ischemia. [13C]Glucose was infused immediately after the reperfusion, and in vivo 1H-detected 13C NMR demonstrated sequential glucose incorporation into the liver. However, the incorporation depended on the blood sugar levels and did not reflect hepatic function. In vitro 13C NMR disclosed the glycogen C-1 signal in the nonischemic group and alanine C-3 and lactate C-3 signals in the ischemic groups. The intensity of glycogen was correlated positively (r = 0.648, P = 0.002) and those of alanine and lactate were correlated negatively (r = -0.831, P < 0.005 and r = -0.710, P = 0.005, respectively) to the ATP levels as measured by in vivo 31P NMR. These results suggested that ATP level participates in glycogenesis and gluconeogenesis in the liver. The AKBR and oxygen consumption of isolated mitochondria were the highest in the 10-min ischemia group, which might reflect mitochondrial compensatory response to the decreased ATP level.

Animals↗

PubMed1996

Acute focal cerebral ischemia in rats studied by diffusion-weighted magnetic resonance imaging--an experimental study.

BACKGROUND: Temporary occlusion of the cerebral artery is occasionally repeated during neurosurgical operations, but the safety of such a procedure remains to be studied further. METHOD: We studied early changes and reversibility of focal cerebral ischemia and the cumulative effects of repeated ischemic insults in rats using magnetic resonance imaging (MRI). RESULTS: Diffusion-weighted magnetic resonance images (DWI) and determination of signal intensity ratio (SIR) proved to be a valuable measure of studying early changes and reversibility of transient focal cerebral ischemia and cumulative adverse effects of repeated ischemic insults. DWIs showed marked intensity changes shortly after focal cerebral ischemia, while T2-weighted images failed to show hyperintensities until 2.5 hours after the onset of permanent ischemia. The critical period of ischemia in this model was 60 minutes. However, 20 minutes ischemia, when repeated twice with 60 minutes reperfusion in between, showed irreversible damage. CONCLUSION: Repeated insults of focal regional cerebral ischemia may cause irreversible tissue damage even if each ischemic period is less than the critical one.

Animals↗

PubMed1996

Lithium side effects in relation to brain lithium concentration measured by lithium-7 magnetic resonance spectroscopy.

1. The relationship between lithium (Li) side effects and brain Li concentration was examined in 17 patients with bipolar disorder treated with Li and other psychotropic drugs. 2. Brain Li concentration was measured by Li-7 magnetic resonance spectroscopy (MRS). Side effects were assessed using the UCLA General Side Effect Rating Scale For Lithium Treatment (GSE). 3. There was no correlation between the total GSE score and the brain, serum, or erythrocyte Li concentrations. Patients with hand tremor had significantly higher brain Li level (0.51 + or - 0.27 mM) than those without apparent tremor (0.36 + or - 0.20 mM), but no significant difference in serum Li level was seen. As far as the patients had hand tremor, they rarely had brain Li concentration less than the therapeutic range (1 of 15 measurement). On the other hand, they often had brain Li levels less than the therapeutic range when they did not have apparent tremor (13 of 52 measurements). 4. This preliminary study suggests that hand tremor is associated with the brain Li concentration.

Adult↗

PubMed1996

Dissociation between lactate accumulation and acidosis in middle cerebral artery-occluded rats assessed by 31P and 1H NMR metabolic images under a 2-T magnetic field.

The relationships among tissue edema, lactate accumulation, and intracellular pH in middle cerebral artery (MCA)-occluded rats were investigated with multiecho 1H magnetic resonance imaging and spatially resolved metabolic images constructed by 1H and 31P nuclear magnetic resonance (NMR) chemical shift imaging (CSI). For the effective and sensitive detection of NMR signals from the brain, outer volume suppression (OVS), reduced k-space sampling and proton irradiation were incorporated into the CSI sequences. The consecutive three measurements of calculated T2 image, lactate image, and pH image which were required for 3.75 h were repeated for four cycles of 1-16 h after MCA occlusion. Tissue edema and lactate accumulation in the infarcted region were gradually and consistently increased during the 15-h observation period. In contrast, severe acidosis was already detected on the first pH image (2-4.7 h after MCA occlusion); thereafter, the degree of acidosis became milder and showed no further progression. The dissociation between the time courses of the lactate accumulation and pH decrease was clearly demonstrated by the NMR metabolic images. Acid-base balance in cerebral infarction might be affected not only by lactate production but also by complicated interactions with tissue edema and some other factors.

Acidosis↗

PubMed1996

Prevalence of cavum septum pellucidum detected by MRI in patients with bipolar disorder, major depression and schizophrenia.

The incidence of cavum septum pellucidum (CSP), which has been widely regarded as a developmental anomaly of little clinical importance in neuropathology, was examined in 113 patients with affective disorders (69 with bipolar disorder and 44 with major depression), 40 schizophrenic patients, and 92 control subjects by magnetic resonance imaging (MRI). Significantly higher incidence of Grade 3-4 CSP (moderate to large) compared with the controls was found only in the schizophrenics. When a broader interpretation of CSP, including indeterminant (Grade 1) and small (Grade 2) CSP was used, three additional patients with bipolar disorder were found to have Grade 1-2 CSP, and the total prevalence of Grade 1-4 CSP in the patients with bipolar disorder was significantly higher than that in the control subjects but slightly lower than that in the schizophrenic patients. CSP was not observed in any patient with major depression. There were no differences between the patients with and without CSP in age, sex, education, or the duration of illness. These findings are consistent with the hypothesis that neurodevelopmental abnormality may be present in schizophrenia, and such an abnormality may also be present in some patients with bipolar disorder.

Adult↗

PubMed1996

Effect of photic stimulation on energy metabolism in the human brain measured by 31P-MR spectroscopy.

Effect of photic stimulation (PS) on energy metabolism in the human occipital cortex was examined by using phosphorus-31 magnetic resonance spectroscopy in 9 normal subjects. Phosphocreatine (PCr)/total phosphorus signal peak area ratio significantly decreased from 12.3% to 10.9% during the 12 minutes of PS (P < 0.05). PCr once returned to a normal level after PS (11.9%) but significantly decreased again 12-18 minutes after PS (10.8%; P < 0.05). Intracellular pH increased from 7.08 to 7.16 during PS, although this increase was not significant. These results suggest that functional alteration of energy metabolism in the brain is different from that in muscles.

Adult↗

PubMed1996

Mechanism of the negative force-frequency relationship in physiologically intact rat ventricular myocardium--studies by intracellular Ca2+ monitor with indo-1 and by 31P-nuclear magnetic resonance spectroscopy.

We studied the subcellular mechanisms of the negative force-frequency relationship in rat myocardium by measuring 1) intracellular Ca2+ transients by indo-1 fluorometry and 2) intracellular pH (pHi) and phosphate compounds with 31P-nuclear magnetic resonance (NMR). The data were compared with those from guinea pig hearts, which show a positive force-frequency relationship. By increasing the pacing rate from 3 Hz to 5 Hz, the peak positive first derivative of left ventricular pressure (LVdP/dt) in rat heart decreased by 10 +/- 1% (n = 6). In contrast to this negative inotropic response, simultaneously measured peak Ca2+ transients increased by 6 +/- 1%. Guinea pig heart (n = 6) showed an increase in peak positive LVdP/dt (33 +/- 1%) which was associated with an increase in peak Ca2+ transients (8 +/- 1%). Under equivalent experimental conditions in an NMR spectrometer, this increase in the pacing rate did not affect intracellular levels of phosphate compounds in either rat (n = 6) or guinea pig heart (n = 6). In contrast, pHi showed a decrease of 0.031 +/- 0.006 pH units in rat heart, while no changes were observed in guinea pig heart. These results suggest that in physiological rat myocardium, pHi is susceptible to changes in the stimulus frequency and may affect the Ca(2+)-responsiveness of contractile proteins, which results in the negative force-frequency relationship.

Animals↗

PubMed1996

Choline-containing compounds detected by proton magnetic resonance spectroscopy in the basal ganglia in bipolar disorder.

Choline-containing compounds (Cho) were examined by proton magnetic resonance spectroscopy (1H-MRS) in the left subcortical region, including basal ganglia, in 19 euthymic patients with bipolar disorder and 19 age-matched normal controls. Ten of the patients were treated with lithium; the remaining 9 were not treated with lithium for at least 30 d. The Cho to creatine + phosphocreatine (Cr) peak ratio in the bipolar patients (0.75 +/- 0.38 [mean +/- SD]) was higher than that in the normal controls (0.52 +/- 0.26, P < 0.05). There was no significant difference in the Cho:Cr peak ratio between patients treated with lithium (0.63 +/- 0.36) and without lithium (0.89 +/- 0.35). These results do not support the hypothesis that lithium increases the brain choline-containing compounds, but rather imply that membrane breakdown may occur in the basal ganglia of patients with bipolar disorder.

Adult↗

PubMed1995

Lateralized abnormality of high-energy phosphate and bilateral reduction of phosphomonoester measured by phosphorus-31 magnetic resonance spectroscopy of the frontal lobes in schizophrenia.

Magnetic resonance spectroscopy (one-dimensional chemical shift imaging) was used to measure membrane phospholipid metabolism and high-energy phosphate metabolism in the left and right frontal lobes of 27 schizophrenic patients. In the schizophrenic patients, the phosphomonoester peak area was decreased in bilateral frontal lobes compared with that in age-matched normal subjects. On the other hand, the peak area of beta-adenosine triphosphate was increased in the left frontal lobe in the schizophrenic group. The phosphocreatine peak area was increased in the left frontal lobe of schizophrenic patients with high scores on the Scale for the Assessment of Negative Symptoms (SANS).

Adenosine Triphosphate↗

PubMed1995

Quantitative measurements of cardiac phosphorus metabolites in coronary artery disease by 31P magnetic resonance spectroscopy.

BACKGROUND: 31P metabolite measurements in the human heart by magnetic resonance spectroscopy (MRS) have been reported previously. By use of a method in which metabolite content was quantified with reference to a standard located outside the chest, it has become possible to measure the content of phosphocreatine (PCr) and ATP in vivo in the human heart. In this study, PCr and ATP contents were measured by 31P MRS and compared in human myocardium with reversible ischemia or scar diagnosed by exercise thallium scintigraphy. METHODS AND RESULTS: Forty-one subjects with stenosis of the left anterior descending coronary artery (> 50%) and 11 healthy control subjects (C) composed the present study group. Patients were divided into two groups on the basis of exercise 201Tl scintigraphy: a reversible 201Tl defect group (RD[+], n = 29) who demonstrated redistribution at late image and a fixed 201Tl defect group (RD[-], n = 12). While the subjects lay supine within the magnet, 31P MR spectra were obtained from the anterior and apical regions of the left ventricle by slice-selected one-dimensional chemical shift imaging. For metabolite quantification, a standard was placed at the center of the surface coil. ANOVA revealed significant differences among the three groups with respect to the mean (+/- SD) PCr at rest (C, 12.14 +/- 4.25 > RD[+], 7.64 +/- 3.00 > RD[-], 3.94 +/- 2.21 mumol/g wet heart tissue, P < .05) as well as a significant decrease in ATP in the RD(-) group (C, 7.72 +/- 2.97; RD[+], 6.35 +/- 3.17 > RD[-], 4.35 +/- 1.52 mumol/g wet heart tissue, P < .05). CONCLUSIONS: Compared with healthy control subjects, PCr content decreased significantly in patients with both reversible and fixed 201Tl defects, and ATP content decreased significantly in subjects with fixed thallium defects. These results suggest that the measurement of ATP content in the human heart by 31P MRS is a clinically important method for the evaluation of myocardial viability.

Adenosine Triphosphate↗