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Biomedical subjects

S Nagase

Publications and source records attributed to S Nagase.

At least 19 recordsLinked to original sources

Effect of spontaneous exercise on antioxidant capacity in rat muscles determined by electron spin resonance.

AIMS: The effect of physical activity on antioxidant capacity in muscle remains unknown. This study investigated the effect of spontaneous exercise on antioxidant capacity in rat muscles determined by electron spin resonance (ESR), which is a technique for the direct detection of free radicals. METHODS: Ten-week-old male Wistar rats were housed individually in cages with a running wheel. Rats were classified as high activity (HA), middle activity (MA) or low activity group (LA), based on an assessment of running distance covered over a 23-week period. After 23 weeks of housing, soleus (Sol), plantaris (Pl), gastrocnemius [deep/surface portions (GasD/GasS)] and heart (Hrt) muscles were isolated, and scavenging activity against superoxide anions (O(2)(*-)) and hydroxyl radicals (HO(*)) was determined by ESR using a spin-trap chemical. The citrate synthase (CS) activity was used as a marker of mitochondrial oxidative phosphorylation capacity. RESULTS: Among the parameters measured, only O(2)(*-) scavenging activity in GasD significantly correlated with the running distance. The highest scavenging activity was observed in Hrt of HA rats. The O(2)(*-) scavenging activity in Pl of MA rats was significantly higher than that of LA rats. The O(2)(*-) scavenging activity of Sol and GasS was not significantly different between the three groups. Furthermore, the HO(*) scavenging activity of any muscle specimens was similar among the three groups and did not correlate with running distance at all. CS activity did not significantly differ between the three groups. CONCLUSION: These data suggest that O(2)(*-) scavenging activity in specific types of muscle tissues would increase especially in spontaneously active animals. However, HO(*) scavenging activity would not.

Animals↗

Nutcracker syndrome associated with severe anemia and mild proteinuria.

A 70-year-old man was referred to our hospital with the chief complaint of gross hematuria. Urinalysis revealed gross hematuria (3+, RBC 100/HPF or more) and mild proteinuria (3+, 1.8 g/day) with no urinary casts. Computed tomography of the abdomen showed compression of the left renal vein between the superior mesenteric artery and the aorta. Ultrasonography showed an increased flow velocity at the stenotic portion of the left renal vein. An aortography and selective left renal arteriography showed that there was no evidence of tumor vessels or arterial abnormalities in the arterial phase. However, the venous phase revealed a stenosis of the left renal vein just lateral to the aorta as well as a reflux of contrast material toward the left gonadal vein which was dilated. In addition, cystoscopy revealed left ureteral bleeding. Based on these findings, we made the diagnosis of gross hematuria caused by nutcracker syndrome (NCS). We concluded that the main cause of the anemia and proteinuria in our patient was leakage of blood and this is confirmed by the relationship of red blood cells to protein in the urine because we proved whole blood and plasma protein loss in the urine by calculation. Fourteen months after discharge, both the gross hematuria and proteinuria spontaneously disappeared. This case strongly suggested that the first therapy for hematuria and proteinuria with NCS should be observation.

Aged↗

The antioxidant EPC-K1 ameliorates brain injury by inhibiting lipid peroxidation in a rat model of transient focal cerebral ischaemia.

BACKGROUND: Cerebral ischaemia-reperfusion injury is associated with the generation of reactive oxygen species during the early phases of reoxygenation. EPC-K1, a phosphate diester of vitamins C and E, has been reported to possess potent hydroxyl radical scavenging activity. This study was performed to investigate the effectiveness of EPC-K1 in attenuating cerebral ischaemia-reperfusion injury in a rat model of transient focal cerebral ischaemia. METHOD: We evaluated the efficacy of EPC-K1 by measuring the concentration of cerebral thiobarbituric acid reactive substances (TBARS), an indicator of the extent of lipid peroxidation by free radicals, and infarct size in rats subjected to one hour of cerebral ischaemia and 4, 24, or 72 hours of reperfusion. FINDINGS: EPC-K1 significantly reduced both the cerebral TBARS level and the infarct size in a rat model of transient focal cerebral ischaemia. These results indicate that EPC-K1 administration during the early stages of reperfusion ameliorates ischaemic brain injury by inhibiting lipid peroxidation. INTERPRETATION: This report is the first to describe the protective mechanism of EPC-K1 by measuring both the TBARS level and infarct size in a rat model of transient focal cerebral ischaemia, and may suggest a potential clinical approach for the treatment of ischaemic cerebrovascular disease.

Animals↗

Glomerular crescents predominantly express cadherin-catenin complex in pauci-immune-type crescentic glomerulonephritis.

AIMS: To investigate the expression of the cadherin complex in human crescentic glomerulonephritis to elucidate the role of intercellular adherens junction molecules in crescent formation. METHODS AND RESULTS: Immunostaining revealed cadherin complexes localized in Bowman's epithelial cells, but not in podocytes, of normal human glomeruli. Eight adult cases with myeloperoxidase anti-neutrophil cytoplasmic autoantibodies (MPO-ANCA)-related (pauci-immune type) crescentic glomerulonephritis were examined on immunofluorescence microscopy with anti-pan cadherin, p120 catenin, and beta-catenin antibodies. The specimens provided six cellular crescents, 12 fibrocellular crescents, and four fibrotic crescents. Immunofluorescence was semiquantitatively estimated by the rate of the field of localization within the whole area of the crescent, according to the four-grade system [(-) - (++)]. All the tested molecules consisting of the cadherin complex were abundantly observed in cytokeratin-positive epithelial components in crescents, each with an equivalent area of localization. The expression of the cadherin complex was closely associated with that of cytokeratin and both diminished as the crescents developed from cellular to fibrotic. CONCLUSIONS: The cadherin-catenin complex is a specific marker of Bowman's epithelial cells in human glomeruli. The cellular crescents in pauci-immune-type crescentic glomerulonephritis possess adherens junction molecules, indicating a principle parietal epithelial cell phenotype.

Adherens Junctions↗

A nonspectroscopic method to determine the photolytic decomposition pathways of 3-chloro-3-alkyldiazirine: carbene, diazo and rearrangement in excited state.

C(60) acts as a mechanistic probe for the formation of carbene, diazo compound, and for the rearranged product via the excited state in the photolysis of 3-chloro-3-isopropyldiazirine and 3-chloro-3-chloromethyldiazirine. The carbene adds to C(60) to form methanofullerene, whereas the diazo compound adds to C(60) to form fulleroid. The olefin product arises as a result of the rearrangement in the excited state.

Journal Article↗

Synthesis, structure, electrochemistry, and spectroelectrochemistry of hypervalent phosphorus(V) octaethylporphyrins and theoretical analysis of the nature of the PO bond in P(OEP)(CH(2)CH(3))(O).

A variety of phosphorus(V) octaethylporphyrin derivatives of the type [P(OEP)(X)(Y)](+)Z(-) (OEP: octaethylporphyrin) (X = CH(3), CH(2)CH(3), C(6)H(5), F; Y = CH(3), CH(2)CH(3), OH, OCH(3), OCH(2)CH(3), On-Pr, Oi-Pr, Osec-Bu, NHBu, NEt(2), Cl, F, O(-); Z = ClO(4), PF(6)) were prepared. X-ray crystallographic analysis of eleven compounds reveals that the degree of ruffling of the porphyrin core becomes greater and the average P-N bond distance becomes shorter as the axial ligands become more electronegative. Therefore, the electronic effect of the axial substituents plays a major role in determining the degree of ruffling although the steric effect of the substituents plays some role. A comparison of the (1)H NMR chemical shifts for the series of [P(OEP)(CH(2)CH(3))(Y)](+)Z(-) complexes with those of the corresponding arsenic porphyrins, which possess a planar core, indicates a much smaller ring current effect of the porphyrin core in the severely ruffled phosphorus porphyrins. The electrochemistry, spectroelectrochemistry and ESR spectroscopy of the singly reduced compounds are also discussed. The OH protons of [P(OEP)(X)(OH)](+) are acidic enough to generate P(OEP)(X)(O) by treatment with aq dilute NaOH. X-ray analysis of P(OEP)(CH(2)CH(3))(O) reveals that the PO bond length is very short (1.475(7) A) and is comparable to that in triphenylphosphine oxide (1.483 A). The features of the quite unique hexacoordinate hypervalent compounds are investigated by density functional calculation of a model (Por)P(CH(2)CH(3))(O) and (Por)P(F)(O) (Por: unsubstituted porphyrin).

Journal Article↗

Mg@C72 MNDO/d evaluation of the isomeric composition.

Temperature development of the relative stabilities of isomers of Mg@C72 (which has not yet been isolated) is computed using the recently introduced MNDO/d method. Four isomers originally considered for the Ca@C72 case are treated: one isolated-pentagon-rule (IPR) structure, two structures with a pair of adjacent pentagons, and one cage with a heptagon. The IPR structure comes as the lowest in MNDO/d potential energy, being rather closely followed by the two structures with a pentagon-pentagon pair. On the other hand, the structure with a heptagon is located too high in potential energy to be of any experimental significance. The entropy contributions are evaluated by the MNDO/d-based partition functions so that the relative concentrations can be treated accordingly. The computations suggest that if Mg@C72 is isolated, it should be a mixture of either two or three isomers. The prediction depends on temperature prehistory. If preparation takes place at temperatures of approximately 1000 K, two isomers should be produced. If temperatures are increased to approximately 2000 K, there will already be three isomers with significant relative concentrations. The study supplies a further interesting example of the profound role of enthalpy-entropy interplay in stabilities of isomeric fullerenic structures.

Carbon↗

Role of nitric oxide in the synthesis of guanidinosuccinic acid, an activator of the N-methyl-D-aspartate receptor.

BACKGROUND: We propose that reactive oxygen and argininosuccinic acid (ASA) form guanidinosuccinic acid (GSA). An alternative to this hypothesis is the so-called guanidine cycle, which consists of a series of hydroxyurea derivatives that serve as intermediates in a pathway leading from urea to GSA. We compare the role of the guanidine cycle to that of nitric oxide (NO) in the synthesis of GSA. METHODS: The members of the guanidine cycle (hydroxyurea, hydroxylamine plus homoserine, L-canaline, and L-canavanine) were incubated with isolated rat hepatocytes. The known NO donors, NOR-2, NOC-7, and SIN-1, were incubated with ASA in vitro. Ornithine, arginine, or citrulline, which increase arginine, a precursor of NO, were incubated with isolated rat hepatocytes. GSA was determined by high-performance liquid chromatography. RESULTS: None of guanidine cycle members except for urea formed GSA. SIN-1, which generates superoxide and NO formed GSA, but other simple NO donors, did not. Both carboxy-PTIO, a scavenger of NO, and dimethyl sulfoxide, a hydroxyl radical scavenger, completely inhibited GSA synthesis by SIN-1. GSA formation by SIN-1 reached a maximum at 0.5 mmol/L and decreased at higher concentrations. GSA synthesis, stimulated by urea in isolated hepatocytes, was inhibited by ornithine, arginine, or citrulline with ammonia, but not by ornithine without ammonia, where arginine production is limited. CONCLUSION: GSA is formed from ASA and the hydroxyl radical. When arginine increased in hepatocytes, GSA synthesis decreased. These data suggest that increased NO, which results from high concentrations of arginine, or SIN-1 scavenges the hydroxyl radical. This may explain the decreased GSA synthesis in inborn errors of the urea cycle where ASA is decreased, and also the diminished GSA excretion in arginemia.

Animals↗

Relatively benign clinical course in asymptomatic patients with brugada-type electrocardiogram without family history of sudden death.

INTRODUCTION: The incidence of sudden death or ventricular fibrillation (VF) in asymptomatic Brugada syndrome patients with a family history of sudden death is reported to be very high. However, there are few reports on the prognosis of asymptomatic Brugada syndrome patients without a family history of sudden death. METHODS AND RESULTS: Eleven patients (all male; mean age 40.5 +/- 9.6 years, range 26 to 56) with asymptomatic Brugada-type ECG who had no family history of sudden death were evaluated. The degrees of ST segment elevation and conduction delay on signal-averaged ECG (SAECG) before and after pilsicainide were evaluated in all 11 patients. VF inducibility by ventricular electrical stimulation also was evaluated in 8 of 11 patients. Patients were followed for a period of 9 to 84 months (mean 42.5 +/- 21.6). The J point level was increased (V1: 0.19 +/- 0.09 mV to 0.36 +/- 0.23 mV; V2: 0.31 +/- 0.12 mV to 0.67 +/- 0.35 mV) by pilsicainide. Conduction delay was increased (total QRS: 112.2 +/- 6.3 msec to 131.7 +/- 6.3 msec; under 40 microV: 42.0 +/- 8.5 msec to 52.7 +/- 12.7 msec; last 40 msec: 17.4 +/- 5.9 microV to 10.4 +/- 6.1 microV) on SAECG by pilsicainide. VF was induced in only 1 of 8 patients. None of the patients had syncope or sudden death during a mean follow-up of 42.5 +/- 21.6 months. CONCLUSION: This study suggests that asymptomatic patients with Brugada-type ECG who have no family history of sudden death have a relatively benign clinical course.

Adult↗

Antimicrobial susceptibility of Staphylococcus intermedius isolated from healthy and diseased dogs.

A total of 90 strains of Staphylococcus intermedius isolated from dogs were examined for antimicrobial susceptibility. There were no significant differences in the distribution patterns of MICs between strains from 1982 to 1985 and those from 1999, and between strains from healthy dogs and those from diseased dogs. All of the strains were susceptible to ABPC, DMPPC, CEX, TDM, ERFX, BFLX, and FF at concentrations of 0.05 to 6.25 microg/ml. The MICs of OTC, KM, EM, AIV-TS, and LCM were distributed in a broad range of 0.1 to >100 microg/ml, indicating the existence of resistant as well as susceptible populations of S. intermedius. Thirty-three strains (36.7%) were resistant to one or more anitmicrobial agents such as OTC (n=32), KM (n=9), EM (n=7), AIV-TS (n=7), and LCM (n=7).

Animals↗

A first photochemical bis-germylation of C60 with digermirane

[reaction: see text]In the photochemical bis-germylation of C60 with 1,1,2,2-tetrakis(2,6-diethylphenyl)-1,2-digermirane (1), a cycloadduct (2) is obtained in high yield for the first time. Spectroscopic analysis and theoretical investigation confirm that 2 (which has C1 symmetry) results from 1,4-cycloaddition. Control experiments and laser flash photolysis experiments suggest that an exciplex intermediate is responsible for the formation of 2. The redox properties of 2 were examined by differential pulse voltammetry.

Journal Article↗

Apolipoprotein E allele-dependent antioxidant activity in brains with Alzheimer's disease.

Thiobarbituric acid-reactive substances (TBARS), an index of lipid peroxidation, were assayed in postmortem brain. Basal TBARS levels were increased and oxidative stimulation produced more TBARS in AD relative to control brains. In addition, apolipoprotein E isoforms showed differing antioxidant activities, with E2 > E3 > E4, suggesting that the lowest antioxidant activity of E4 could contribute to its association with AD.

Aged↗

Changes in cochlear electrical stimulation induced Fos expression in the rat inferior colliculus following deafness.

Fos immunoreactive (IR) staining was used to examine changes in excitatory neuronal activity in the rat inferior colliculus (IC) between normal hearing and 21 day deaf rats evoked by basal or apical monopolar cochlear electrical stimulation. The location of evoked Fos IR neurons was consistent with expected tonotopic areas. The number of Fos IR cells increased as stimulation intensity increased in both normal and 21 day deaf animals. Stimulation at 1. 5x threshold evoked fewer Fos IR cells in 21 day deafened animals compared to normal hearing animals. At 5x and above, however, significantly increased numbers of Fos IR neurons (in a larger grouping) were evoked in 21 day deafened animals compared to normal hearing animals. Another group of animals had 7 days of deafness followed by 14 days of chronic basal cochlear electrical stimulation. In this group basal monopolar stimulation at 5x evoked not only a greater number of Fos IR neurons, compared to normal hearing animals, but the location of their grouping was slightly shifted to a more dorso-lateral region in the contralateral IC, compared to the normal hearing and 21 day deaf groups. These observations indicate that both deafness and chronic electrical stimulation may alter central auditory processing.

Animals↗

Creatol, an oxidative product of creatinine in hemodialysis patients.

Creatol (CTL) is a product resulting from the reaction of creatinine (Cr) with the hydroxyl radical and is identified as a precursor of methylguanidine (MG), a uremic toxin. In this study, we investigated serum CTL levels together with those of Cr and MG in 66 patients who were on maintenance hemodialysis (HD). Prior to dialysis, the mean serum levels of Cr, CTL and MG were 967 (= 11.1 mg/dl)+/-267 microM, 11.1+/-4.8 microM and 5.8+/-2.9 microM, respectively. The mean CTL level was about 1.1% that of Cr, and the CTL plus MG level was about 1.4% that of the Cr level. The reduction rates of Cr, CTL and MG by a single HD were 62.6 6.1%, 71.0+/-10.3% and 51.9+/-11.6%, respectively. The CTL level at 0.5, 1 and 6 h after HD increased rapidly by 20.7+/-8.7%, 31.7+/-14.7% and 80.1+/-27.3%, respectively. There was a significant correlation between CTL or CTL/Cr and parathyroid hormone in patients who had just undergone parathyroidectomy. No significant correlation was found between CTL or CTL/Cr and those factors which seems to be related to the predialysis levels of reactive oxygen. Therefore, because of the good clearance of CTL and its rapid conversion to MG, its usefulness for the estimation of hydroxyl radical generation in HD patients is limited.

Adult↗