Biomedical subjects

T Inubushi

Publications and source records attributed to T Inubushi.

At least 37 records · Page 2Linked to original sources

PubMed1999

Renal ischemia/reperfusion remotely improves myocardial energy metabolism during myocardial ischemia via adenosine receptors in rabbits: effects of "remote preconditioning".

OBJECTIVES: This study examined the changes in myocardial energy metabolism during myocardial ischemia after "remote preconditioning" and investigated the involvement of adenosine receptors in the mechanisms of this effect. BACKGROUND: Recent studies have indicated that a brief period of ischemia and reperfusion (ischemic preconditioning, PC) in a remote organ reduces myocardial infarct size (IS) protecting against subsequent sustained myocardial ischemia. However, the mechanisms of "remote PC" remain unclear. We assessed myocardial energy metabolism during sustained myocardial ischemia and reperfusion after renal PC (RPC), in comparison with that after myocardial PC (MPC) in open-chest rabbits. It has been established that adenosine receptors are involved in the mechanisms of MPC. METHODS: Rabbits that had been anesthetized with halothane were divided into six groups. The control (CNT) group underwent 40-min coronary occlusion followed by 120 min reperfusion. Before the procedure, the MPC group underwent an additional protocol of 5 min coronary artery occlusion and 20 min reperfusion, and the RPC group received a 10 min episode of renal artery occlusion and 20 min reperfusion. In additional experimental groups, 8 sulfophenyl-theophylline (SPT, 10 mg/kg), an adenosine receptor inhibitor, was intravenously injected before the 40 min myocardial ischemia (SPT, MPC + SPT and RPC + SPT groups, respectively). Myocardial levels of phosphocreatine (PCr), ATP and intracellular pH (pHi) were measured by 31P-NMR spectroscopy. RESULTS: RPC and MPC delayed the decreases in ATP levels, preserved pHi during 40-min myocardial ischemia and resulted in better recovery of ATP and PCr during 120 min reperfusion compared with the controls. SPT abolished the improvement in myocardial energy metabolism and the reduction in myocardial IS caused by MPC or RPC. Myocardial IS in the CNT (n = 8), MPC (n = 9), RPC (n = 9), SPT (n = 6), MPC + SPT (n = 8) and RPC + SPT (n = 8) groups averaged 42.8+/-3.5%, 18.2+/-1.8%*, 19.6+/-1.3%*, 44.9+/-5.0%, 35.6+/-2.7% and 34.8+/-3.6% of the area at risk (*p < 0.05 vs. CNT), respectively. CONCLUSIONS: PC in a remote organ, similar to MPC, improved myocardial energy metabolism during ischemia and reperfusion and reduced IS in vivo by an adenosine-dependent mechanism in rabbits.

Adenosine Triphosphate↗

PubMed1999

Quantitative proton magnetic resonance spectroscopy of the bilateral frontal lobes in patients with bipolar disorder.

BACKGROUND: Using 31P and 1H magnetic resonance spectroscopy (MRS) we previously reported that phosphocreatine was decreased in the left frontal lobe and choline-containing compounds were increased in the basal ganglia in the depressive state in patients with bipolar disorder. We applied quantitative 1H-MRS for further characterization of biochemical alteration in the frontal lobes of bipolar patients. METHODS: Twenty-three bipolar patients and 20 normal controls were examined by 1H-MRS with a 1.5T MR system. All patients were examined in the euthymic state, and eight patients were also examined in the depressive state. Volumes of interest of 2.5 x 2.5 x 2.5 cm were selected in the left and right frontal lobes. Absolute concentrations of N-acetyl-1-aspartate, creatine plus phosphocreatine, and choline-containing compounds were calculated from each metabolite peak. RESULTS: Creatine concentration in the left frontal lobe in bipolar patients in the depressive state was significantly lower than that in the euthymic state. Creatine concentration in the right frontal lobe in the male patients was significantly higher than that in the female patients and a similar trend was also found in the control subjects. CONCLUSIONS: We found a state-dependent change of creatine metabolism in the left frontal lobe of bipolar patients. The present results are compatible with our previous report of decreased phosphocreatine measured by 31P-MRS in the left frontal lobe in bipolar disorder. We also found an effect of gender on the creatine concentration. There may be a gender difference in creatine transport function into the brain.

Adult↗

PubMed1999

Relationship of energy metabolism detected by 31P-MRS in the human brain with mental fatigue.

To search for a possible relationship between brain energy metabolism and mental fatiguability, 10 normal volunteers were examined by 31P-MRS (phosphorus-31 magnetic resonance spectroscopy) in the occipital cortex during photic stimulation (PS), and Uchida-Kraepelin test (UKT), a standardized serial calculation task, was used for measurement of intraindividual characteristics of mental fatigue in these subjects. More decrease of phosphocreatine measured by 31P-MRS during the PS was significantly associated with more effects of rest assessed by UKT (r = -0.86, p <0.005). More decrease in pH after PS was associated with steeper decline of performance (r = 0.78, p <0.01). These findings suggest that characteristics of brain energy metabolism in an individual may relate to intrinsic patterns of mental fatigability.

Adult↗

PubMed1999

Noninvasive evaluation of the malignant potential of intracranial meningiomas performed using proton magnetic resonance spectroscopy.

OBJECT: Controversy exists about correlations between histological tumor grade and magnetic resonance (MR) spectroscopy data. The authors studied single-voxel proton MR spectroscopy as a noninvasive way to evaluate grade of malignancy in intracranial meningiomas. METHODS: The authors compared the results of MR spectroscopy with those derived by the MIB-1 staining index (SI) in 29 meningiomas. Proton MR spectroscopy was performed using stimulated echo acquisition and volume-localized solvent-attenuated proton nuclear MR sequences before surgery or other therapy. Twenty-four tumors were histologically benign (13 meningothelial, three fibrous, four transitional, three angiomatous, and one chordoid); four were atypical (Grade II), and one was papillary (Grade III). The mean MIB-1 SI in the benign group was significantly lower than those in the other groups (p = 0.0041). The mean choline-containing compound (Cho)/ creatine and phosphocreatine (Cr) ratios in the benign and nonbenign groups were 2.56+/-1.26 and 7.85+/-3.23, respectively (p = 0.0002). A significant linear correlation was observed between the Cho/Cr ratio and the MIB-1 SI (r0.05 = 0.74, p<0.001). Necrosis was present histologically in four of the five meningiomas classified either as atypical or papillary. Magnetic resonance spectroscopy revealed a methylene signal in these meningiomas that was not detected in benign meningiomas. Of the five meningiomas in which only a lactate signal was observed, two were benign and the MIB-1 SI in these two benign meningiomas was higher than the mean value for the benign group. Alanine, detected in 12 of 30 meningiomas, did not correlate with either tumor grade or Cho/Cr ratio. CONCLUSIONS: Proton MR spectroscopy is a useful diagnostic method for determining the proliferative or malignant potential of meningiomas according to the Cho/Cr ratio. A lactate and/or methylene signal suggests a high-grade tumor.

Adult↗

PubMed1998

A primitive pathway of porphyrin biosynthesis and enzymology in Desulfovibrio vulgaris.

Culture of Desulfovibrio vulgaris in a medium supplemented with 5-aminolevulinic acid and L-methionine-methyl-d3 resulted in the formation of porphyrins (sirohydrochlorin, coproporphyrin III, and protoporphyrin IX) in which the methyl groups at the C-2 and C-7 positions were deuterated. A previously unknown hexacarboxylic acid was also isolated, and its structure was determined to be 12, 18-didecarboxysirohydrochlorin by mass spectrometry and 1H NMR. These results indicate a primitive pathway of heme biosynthesis in D. vulgaris consisting of the following enzymatic steps: (i) methylation of the C-2 and C-7 positions of uroporphyrinogen III to form precorrin-2 (dihydrosirohydrochlorin); (ii) decarboxylation of acetate groups at the C-12 and C-18 positions of precorrin-2 to form 12,18-didecarboxyprecorrin-2; (iii) elimination of acetate groups of the C-2 and C-7 positions of 12,18-didecarboxyprecorrin-2 to form coproporphyrinogen III; and (iv) conversion of coproporphyrinogen III to protoporphyrin IX via protoporphyrinogen IX. We isolated the following three enzymatic activities involved in steps i-iii from the soluble fraction of the cells by anion-exchange chromatography: S-adenosyl-L-methionine:uroporphyrinogen III methyltransferase, precorrin-2 12,18-acetate decarboxylase, and 12, 18-didecarboxyprecorrin-2 2,7-decarboxymethylase; all enzymic products were converted into autooxidized methyl esters and analyzed by thin-layer chromatography, UV-visible (UV-VIS) absorption, and mass spectrometry. The enzymatic reactions in D. vulgaris shed new light on porphyrin biosynthesis at an early stage in the evolution of prokaryotes.

Chromatography, Thin Layer↗

PubMed1998

Measurement of local cerebral blood flow by magnetic resonance imaging: in vivo autoradiographic strategy using 17O-labeled water.

Local cerebral blood flow (LCBF) was measured in cats by magnetic resonance imaging (MRI), using 17O-labeled water (H[2]17O) as a tracer. Cat brain images were obtained using a 256 x 240 matrix fast spin-echo sequence with a total acquisition time of 124 seconds per image. Intravenous injection of H(2)17O and sampling of arterial blood were simultaneously performed during the MRI scan. Injection of H(2)17O over 40 seconds caused a transient decrease in brain signal intensity, from which the changes in H(2)17O concentration of brain tissue were calculated. The concentration of H(2)17O in arterial blood was measured directly by 17O nuclear magnetic resonance (NMR) spectroscopy, and used as an input function for the calculation of LCBF. LCBF was successfully determined using an in vivo autoradiographic strategy in a total of three cats. In one, LCBF measurements were also performed under hypercapnic conditions, and LCBF maps of the cat brain during normocapnia and hypercapnia were constructed. These LCBF maps reflected well the changes in LCBF induced by hypercapnia, which indicated the validity of the used method.

Animals↗

PubMed1998

Photic stimulation-induced alteration of brain energy metabolism measured by 31P-MR spectroscopy in patients with MELAS.

We examined brain energy metabolism by phosphorus-31 magnetic resonance spectroscopy (31P-MRS) in the occipital cortex in a mother and a daughter with MELAS (mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes) during photic stimulation. The peak area ratio of phosphocreatine markedly decreased during photic stimulation, and subsequently increased after the stimulation. This method, photic stimulation-31P-MRS, may be useful in assessing brain energy metabolism in neurological diseases.

Adult↗

PubMed1998

Gluconeogenesis and phosphoenergetics in rat liver during endotoxemia.

BACKGROUND: During endotoxemia, glucose and energy metabolism varies depending on the stage, severity, and other conditions. In this study, gluconeogenesis from 13C-labeled alanine and phosphoenergetic state in rat liver during the acute phase of endotoxemia were concurrently observed by in vivo 13C and 31P NMR spectroscopy in a noninvasive manner. MATERIALS AND METHODS: Lipopolysaccharide from Escherichia coli (10 mg/kg) was injected intravenously followed by infusion of [3-13C]alanine. In vivo 13C and 31P NMR spectra were alternately collected for 90 min with a 2.0 Tesla CSI Omega System. RESULTS: In our experimental model, endotoxin increased the pulse rate without decreasing the blood pressure and elevated the blood sugar level, which suggests the so-called hyperdynamic state. Even under such conditions, a slight, but significant, impairment of the phosphoenergetic state in the liver (a decrease in ATP and an increase in Pi) was detected with 31P NMR spectroscopy. The 13C peaks of glucose C6 and Glu/Gln C2 of the liver in endotoxemia were significantly lower than those of the control, despite hyperglycemia in endotoxemia. CONCLUSIONS: NMR spectroscopic studies suggest that the endotoxin caused the inhibition of gluconeogenic activity from the infused [3-13C]alanine and the TCA cycle accompanied by a deterioration in the phosphoenergetic state even in the hyperglycemic phase. Since the blood sugar level might be influenced by the systemic utilization of glucose, such direct measurements should prove important in the in vivo evaluation of glucose and energy metabolism in the liver.

Adenosine Triphosphate↗

PubMed1998

Influence of aging or left ventricular hypertrophy on the human heart: contents of phosphorus metabolites measured by 31P MRS.

Although both aging and hypertrophy are extremely important factors for cardiac performance, their influence on cardiac metabolism, especially that of high-energy phosphates, has not been fully elucidated as yet. Quantitative measurements of high-energy phosphates were attempted by comparing myocardial 31P NMR spectra with an external reference using depth-resolved surface-coil spectroscopy. The voxel size of the region of interest (ROI) was disk-shaped with 15-cm diameter and 25-mm thickness, but the left ventricular weight actually involved in the ROI was estimated to be between 22 and 66 g using MRI. Myocardial phosphocreatine (PCr) content and adenosine triphosphate (ATP) content for the 30 normal volunteers showed significant age dependence since both decreased in relation to increasing age. Myocardial PCr content and ATP content in patients with hypertension did not differ significantly from the age-matched control group. PCr content (6.1 +/- 2.2 micromol/g wet tissue, n = 10) and ATP content (4.1 +/- 1.3 micromol/g wet tissue) in patients with hypertrophic cardiomyopathy were less than the age-matched control group (n = 15; PCr: 9.7 +/- 2.5 micromol/g wet tissue, P < 0.01; ATP: 6.4 +/- 1.8 micromol/g wet tissue, P < 0.05), respectively. These results indicate that quantitative 31P MRS may be valuable in the assessment of changes in high-energy phosphate metabolism caused by aging or hypertrophy.

Adenosine Triphosphate↗

PubMed1998

Decreased brain intracellular pH measured by 31P-MRS in bipolar disorder: a confirmation in drug-free patients and correlation with white matter hyperintensity.

The authors have previously reported decreased intracellular pH (pHi) in the frontal lobes in euthymic bipolar patients treated with lithium using 31P-MRS. White matter hyperintensity (WMHI) is frequently seen in bipolar disorder. To examine a possible effect of lithium on pHi and the relationship between pHi and WMHI, seven drug-free euthymic bipolar patients were examined, and T2-weighted MRI were examined in 14 previously reported bipolar patients. Drug-free patients showed significantly lower pHi than controls. WMHI was associated with low pHi and increased phosphodiester peak. These results suggest that decrease of pHi is not an effect of lithium but is instead related to the pathophysiology of illness. Decrease of pHi and increase of the PDE peak may be the biochemical basis of WMHI in bipolar disorder.

Adult↗

PubMed1998

Estimation of volume doubling time and cell loss in an experimental rat glioma model in vivo.

We estimated the volume doubling time (Vd) of the ethyl-nitrosourea-induced rat glioma by serial magnetic resonance imaging, and the results were compared with potential doubling time (Tp) determined immunohistochemically. Vd ranged from 3.3 to 29.2 days (11.3 +/- 7.74) and Tp ranged from 2.3 to 13.3 days (6.81 +/- 3.33). Each tumour showed a wide range of bromodeoxyuridine (BUdR) labelling indices (LI), however, Vd and Tp correlated well with BUdR-LI. Vd was estimated as 17.6 x BUdR-LI-0.63 (R = -0.76, P < 0.001, n = 13) and Tp was estimated as 22.6 x BUdR-LI-1.02 (R = -0.92, P < 0.0001, n = 12). In addition, we compared the apoptotic indices (AI), determined by terminal deoxynucleotidyltransferase (Tdt)-mediated biotinylated dUTP-biotin nick-end labelling (TUNEL) techniques, with BUdR-LI and mitoses indices (MI). The results were: AI = 0.23 + 0.25Ln(BUdR-LI) (R = 0.971, n = 8, P < 0.0001) and AI = 1.05 + 0.29Ln(MI) (R = 0.937, n = 8, P < 0.001). Cell loss factors (CLF) also correlated well with BUdR-LI and MI. However, CLF calculated from Tp and Vd were lower than the values previously presumed, probably because of shorter Vd than true doubling time for tumour cell population. These results suggest that even malignant tumours retain a mechanism of adjusting their growth at least partly.

Animals↗

PubMed1998

Novel physiological functions of cathepsins B and L on antigen processing and osteoclastic bone resorption.

Lysosomal cathepsin B plays an essential role in the processing of ovalbumin as an exogenous antigen to produce the complex between antigenic-peptide and major histocompatibility-complex class II. Administration of cathepsin B inhibitors, E-64, CA-074 and vitamin B6, caused the strong suppression of the Th-2 type immune responses. We found that pyridoxal phosphate (PAP), a coenzyme form of vitamin B6, inhibits the activities of cathepsin B and L in vitro and vitamin B6 administration induces the inhibition of the lysosomal cathepsin activities in vivo. The production of an antigenic epitope (I323-R339) of ovalbumin by antigen presenting cells was suppressed by cathepsin B specific inhibitors. The ovalbumin dependent production of immunoglobulins (IgE and IgG1) and of the corresponding interleukin (IL-4) was suppressed by cathepsin B inhibitors, while the production of IgG2a and interferon (INF-gamma) was increased. The switch of helper T lymphocyte functions from the type-2 to the type-1 may be induced by the cathepsin B inhibition. The experimental bone pit formation, i.e., osteoclastic bone collagen degradation test, induced by parathyroid hormone was markedly suppressed by the administration of pyridoxal, because of the inhibition of cathepsin L type cysteine proteases in bone.

Animals↗

PubMed1998

Estrogen protects against while testosterone exacerbates vulnerability of the lateral striatal artery to chemical hypoxia by 3-nitropropionic acid.

Gender differences in the vulnerability of the lateral striatal artery (1STR artery) to systemic intoxication with 3-nitropropionic acid (3-NPA, succinate dehydrogenase inhibitor) were studied. Subcutaneous injection of 3-NPA (20 mg/kg once a day for 2 days) induced striatal selective lesions in half of male rats associated with motor symptoms (rolling, paddling, recumbency, etc) while female rats were resistant. Lesions were located in the lateral striata and characterized by astroglial necrotic cell death, enhanced immunoreaction to factor VIII-related antigen, edema, extravasation of IgG and sometimes bleeding. The motor and histological disturbances were highly sex-dependent and modulated by changes in hormonal levels. Males were more susceptible than females. Castration had little effect but ovariectomy enhanced the vulnerability. Replacement therapy with testosterone increased while estradiol or tamoxifen suppressed the vulnerability in ovariectomized females. Investigation of the arterial architecture of the brain often revealed rectangular and acute angled branchings in the centrolateral striatum where the ISTR artery feeds. A parallel in vitro toxicity study demonstrated that an extreme Ca++ overload and a strong cellular swelling resulted in astrocytic cell death. Data suggest that 1STR artery and astrocytes are highly vulnerable to 3-NPA intoxication in males. The greater vulnerability of the ISTR artery may contribute to the pathogenesis of neurodegenerative diseases, striatal bleeding, etc. Protective effects of estrogen and tamoxifen may mediate gender differences often observed in these disorders and suggest their potential use as therapeutic agents for these disorders.

Animals↗

PubMed1998

Hepatic energy metabolism during ketamine and isoflurane anaesthesia in haemorrhagic shock.

The effects of ketamine and isoflurane on the phosphoenergetic state of the liver during haemorrhage were investigated using 31P nuclear magnetic resonance (NMR) spectroscopy. Male Wistar rats were anaesthetized with ketamine (1.0 mg kg-1 min-1 i.v., Ket 1.0 group, or 1.5 mg kg-1 min-1 i.v., Ket 1.5 group), or isoflurane 1.4% (Iso group). Haemorrhage was induced by withdrawing blood until the mean arterial pressure was reduced to 40 mm Hg, and this pressure level was then maintained for 45 min. Hepatic energy metabolism was evaluated from the changes in adenosine triphosphate (ATP) and inorganic phosphate (Pi). The beta-ATP decrease and the Pi increase were more marked in the two Ket groups than in the Iso group. At 20 min after haemorrhage, the beta-ATP peak areas were 34%, 32% and 76%, and the Pi peak areas were 257%, 260% and 160% of their initial values in the Ket 1.0, Ket 1.5 and Iso groups, respectively. NMR data were supported by chemical assessments. These results demonstrated that, in terms of phosphoenergetic levels, a continuous administration of 1.0 or 1.5 mg kg-1 min-1 ketamine markedly decreased hepatic metabolism during haemorrhagic shock, whereas inhalation of 1.4% isoflurane mitigates the metabolic damage.

Adenosine Triphosphate↗

PubMed1998

Evaluation of focal cerebral ischemia in rats by magnetic resonance imaging and immunohistochemical analyses.

Correlation of focal ischemia-induced brain damage evidenced by magnetic resonance imaging (MRI) and by staining with microtubule-associated protein 2 (MAP2) was studied in rats. Ischemia was produced by transient occlusion of the middle cerebral artery (MCAO). The damage was assessed at 6 to 8 hours after MCAO and 1 week later. The area of damage assessed by MRI agreed with that by MAP2 staining at 6 to 8 hours after MCAO, which was smaller (P < 0.001) than that defined by MAP2 staining 1 week after MCAO. Glial staining indicated that glial infiltration affected the signal intensity of MRI in the area of damage.

Animals↗

PubMed1998

Magnetic resonance spectroscopy in affective disorders.

Magnetic resonance spectroscopy (MRS) is a non-invasive tool for in vivo chemical analysis that has been applied to neurobiological or psychopharmacological studies of affective disorders. Studies employing 31P-MRS and 1H-MRS have indicated possible abnormalities in membrane phospholipid metabolism, high-energy phosphate metabolism, and intracellular pH in affective disorders. They have also suggested that lithium increases the phosphomonoester (possibly inositol-1-phosphate) peak in the brain but does not increase that of choline-containing compounds in the brain. Studies employing 7Li-MRS and 19F-MRS have elucidated the pharmacokinetic properties of lithium, fluoxetine, and fluvoxamine in the brain in patients treated with these drugs.

Affect↗

PubMed1997

Multiple regression analysis of relationship between frontal lobe phosphorus metabolism and clinical symptoms in patients with schizophrenia.

We investigated the differences among diagnostic types of 36 schizophrenic patients in the brain phosphorus metabolism in the frontal lobe. We performed phosphorus-31 magnetic resonance spectroscopy (31P-MRS) in the frontal region in patients with schizophrenia of the catatonic (n = 4), disorganized (n = 8), paranoid (n = 10) and undifferentiated (n = 14) types. In the disorganized type, the PME level was significantly decreased compared to those in the other three types, while the phosphodiester (PDE) level tended to be higher, although not significantly, than those in the other types. Using multiple regression analysis, we investigated whether or not the clinical symptoms were correlated with the brain phosphorus metabolism. An increased motor retardation factor score was significantly correlated with decreased PME level, whereas more severe emotional withdrawal and blunted affect were associated with increased PDE level. These results suggest that altered membrane phospholipid metabolism in the frontal region may be associated with negative symptoms and that schizophrenia of the disorganized type is associated with more severe negative symptoms and may present more severe brain abnormalities compared to the other types.

Adolescent↗

PubMed1997

T2*-weighted magnetic resonance imaging of cerebrovascular reactivity in rat reversible focal cerebral ischemia.

Cerebrovascular carbon dioxide (CO2) reactivity is an important hemodynamic index in cerebrovascular disease. In the present study T2*-weighted magnetic resonance image (T2* WI) was evaluated as a non-invasive method to investigate changes in CO2 reactivity. Fourteen rats were subjected to permanent or, 30 and 90 min of temporary middle cerebral artery occlusion. A series of T2* WIs and diffusion-weighted magnetic resonance images (DWI) was performed hourly under normo- and hypercapnic conditions. Triphenyltetrazolium chloride (TTC) staining of brain sections was obtained at the end of experiment to evaluate ischemic damage. During ischemia, a 4-6% signal increase upon hypercapnia was observed on T2* WI in the non-ischemic hemisphere, while no such reactivity was seen in the putamen and cortex ipsilateral to the MCA occlusion. After reperfusion, CO2 reactivity recovered in the putamen and cortex in the 30 min ischemia group and in the cortex alone of the 90 min ischemia groups. The areas with irreversible CO2 reactivity dysfunction coincidentally revealed no recovery on DWI and lack of TTC staining. The results indicate that T2* WI can be used to monitor changes in CO2 reactivity after various ischemic insults that may indicate tissue viability.

Animals↗