Effects of antiepileptic drugs on sodium channel in rat brain.
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Animals↗
Biomedical subjects
M Mino
Publications and source records attributed to M Mino.
Allelic heterogeneity in group A xeroderma pigmentosum.
The molecular basis of Group A xeroderma pigmentosum was investigated by restriction fragment length polymorphism analysis of PCR-amplified DNA sequences using the two restriction enzymes, endonucleases AlwN I and Hph I. The clones of a patient with Group A xeroderma pigmentosum who had typical symptoms showed a G-C substitution at the 3' splice acceptor site of intron 3. However, of the two atypical Group A xeroderma pigmentosum patients with mild skin lesions and minimal neurological abnormalities, the milder one showed homozygosity for the nonsense mutation of exon 6, while the other patient with slightly greater central nervous involvement was shown to be a compound heterozygote for the splicing mutation of intron 3 and the nonsense mutation of exon 6, thus indicating an allelic heterogeneity in group A xeroderma pigmentosum.
Adolescent↗
Increased glycated Cu,Zn-superoxide dismutase levels in erythrocytes of patients with insulin-dependent diabetis mellitus.
Our previous study indicated that erythrocyte Cu,Zn-superoxide dismutase (Cu,Zn-SOD) undergoes glycation and inactivation in vivo (1) and in vitro (2). The aim of the present study was to assess glycated Cu,Zn-SOD in patients with insulin-dependent diabetes mellitus. Glycated Cu,Zn-SOD, which binds to a boronic acid affinity column, was measured by the enzyme-linked immunosorbent assay. The percentage of the glycated form in 25 insulin-dependent diabetic children was 40.2 +/- 8.2%; this was significantly higher than that in the normal controls (P less than 0.01). The specific activity of the glycated form in the diabetic children was 163,000 +/- 33,000 IU/mg Cu,Zn-SOD protein, significantly lower than that in controls (P less than 0.01). These data indicate that glycated and less active Cu,Zn-SOD is increased in erythrocytes of patients with insulin-dependent diabetes mellitus.
Adult↗
Effect of alpha-tocopherol on oxidative hemolysis, as evaluated by impedance measurement.
Using a hypoxanthine-xanthine oxidase (HX-XOD) reaction system, the effect of vitamin E (VE) on oxidative membrane injury was studied by the impedance method. Both VE-sufficient and VE-deficient erythrocytes showed an elevation of low frequency permittivity in the early phase of reaction. In the later phase of reaction, VE-sufficient erythrocytes showed a sustained elevation in permittivity, while VE-deficient erythrocytes showed a decrease in permittivity with time. These changes consisted with the process of hemolysis in the HX-XOD system. The similarity of early phase change between VE-sufficient and VE-deficient erythrocytes indicates that the HX-XOD system exerted a similar effect on both erythrocytes in the early phase. The difference in changes of later phase between the two types of erythrocytes suggests that VE suppressed the reduction in permittivity. When the results were analyzed by the Pauly-Schwan's theory based on the assumption that erythrocytes are spherical, the product of VE-deficient or VE-sufficient erythrocyte size (R) and membrane capacity (Cm) showed a change similar to that in permittivity.
Algorithms↗
Distribution of circulating beta-carotene in human plasma lipoproteins.
We examined the distribution of beta-carotene in plasma lipoprotein fractions. In healthy children and adults, LDL contained more beta-carotene than did HDL, but in cord blood more beta-carotene was found in HDL than in LDL. After the oral administration of beta-carotene, its plasma level rose although its distribution in the individual lipoprotein fractions did not change. Among disease conditions associated with hyperlipidemia, the ratio of beta-carotene to plasma lipids was highest in anorexia nervosa, while nephrotic syndrome and diabetes mellitus had similar ratios to each other.
Adolescent↗
Bioavailability of vitamins--an overview.
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Ascorbic Acid↗
Changes in plasma levels of vitamin D and its metabolites in healthy subjects after oral administration of vitamin D2.
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Administration, Oral↗
Blood levels and urinary excretion of thiamin and riboflavin during oral administration of multivitamin tablets to healthy adults.
1. The baseline blood thiamin concentration increased gradually during the long-term administration of TTFD, and the blood concentration was dose-dependent. The cumulative urinary thiamin excretion showed the same dose-dependence as the blood concentration. 2. The baseline blood riboflavin concentration also increased steadily during the administration period, but the increase was less than that of thiamin. Dose-dependence of the cumulative urinary excretion of riboflavin was noted. 3. No side effect were observed.
Administration, Oral↗
Vitamin E status in children-health and diseases.
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Erythrocytes↗
Clinical uses and abuses of vitamin E in children.
The major benefits arising from elevated dosages of vitamin E have been the relief of symptoms of vitamin E deficiency in humans with abetalipoproteinemia and chronic cholestasis. In addition, supplements of vitamin E prevent the isolated vitamin E deficiency that has recently been associated with spinocerebellar symptoms. In keeping with the view that newborn infants, and especially premature infants, suffer from vitamin E deficiency, elevated dosages of vitamin E have been administered to prevent the anemia of premature infants, retrolental fibroplasia, bronchopulmonary dysplasia, and intraventricular hemorrhage. However, the results have been conflicting. Furthermore, some infants treated with vitamin E die unexpectedly. The life-threatening hazard of such treatments has been attributed mainly to polysorbates that are used as detergents in preparations of vitamin E for intravenous use rather than to vitamin E itself. The possibility that vitamin E, in its action as an antioxidant, inhibits the generation of superoxide anion in leukocytes is examined in this paper.
Child↗
A case of hypersensitivity syndrome resembling Langerhans cell histiocytosis during phenobarbital prophylaxis for convulsion.
The case of a two-year-old girl with generalized histiocytosis, probably induced by phenobarbital, is reported. Symptoms, including intermittent fever, systemic lymphadenopathy, maculopapular skin eruption and hepatosplenomegaly, suggested Langerhans cell histiocytosis. Laboratory examinations revealed leukocytosis with lymphocytosis and eosinophilia and a high LDH serum level, while GOT and GPT were within normal ranges. Cytological studies of lymph node and pleural effusion specimens revealed proliferation and infiltration of Langerhans cell histiocytes with eosinophilia. No histiocyte proliferation was observed in the bone marrow or skin. The clinical manifestations shown by the patient were, however, transient, and improved spontaneously after the discontinuation of phenobarbital. The case was considered to be one of phenobarbital hypersensitivity syndrome based on clinical course and laboratory findings. The mechanism and differential diagnosis of the syndrome are discussed.
Child, Preschool↗
Vitamin E inhibits PGE2 and O2- production in rat peritoneal macrophages.
In order to examine the possible role of vitamin E on the modulation of macrophages, we investigated the effect of vitamin E on O2- and PGE2 production in macrophages. The production of both PGE2 and O2- in rat peritoneal macrophages was dose-dependently stimulated by the addition of PMA and calcium ionophore A23187. However, the macrophages obtained after intraperitoneal injection of vitamin E for six successive days showed less PGE2 and O2- production when stimulated with PMA or A23187 as compared to those of control macrophages. O2- production in control macrophages stimulated with 139 nM PMA and 1 microM A23187 as 4.2 +/- 0.3 and 3.0 +/- 0.2 nmol/min per 10(6) cells, respectively. On the other hand, O2- production by the macrophages from vitamin E-treated rats was 1.5 +/- 0.4 nmol/min per 10(6) cells when stimulated with the PMA, and was not detectable when stimulated with A23187. As for the production of PGE2, control macrophages produced 2.59 +/- 0.70 ng/30 min per 10(6) cells when stimulated with PMA and 8.96 +/- 3.26 ng/30 min per 10(6) cells with the A23187, whereas PGE2 production by the macrophages from vitamin E-treated rats was reduced to 12-20% of the control. By analyzing alpha-tocopherol content and intracellular concentration of calcium ion [( Ca2+]i) in the macrophages isolated from control and vitamin E-treated rats, vitamin E treatment augmented alpha-tocopherol content (384.7 +/- 76.1 vs. 1.2 +/- 0.4 ng/10(6) cells) and decreased free [Ca2+]i when stimulated with A23187 (652 +/- 14 vs. 1201 +/- 223 nM).
Animals↗
The effect of alpha-tocopherol as an antioxidant on the oxidation of membrane protein thiols induced by free radicals generated in different sites.
Azo compounds enable us to generate peroxyl radicals by thermal decomposition at a constant rate and at a desired site, that is, water-soluble compounds produce initiating radicals in an aqueous phase and lipid-soluble compounds initiate the oxidation within the membrane-lipid layer. Using these radicals generated in different sites, we oxidized red blood cell ghost membranes to study the relationships between alpha-tocopherol depletion, initiation of lipid peroxidation, and protein damage. When radicals were generated in the aqueous phase, the loss of membrane protein thiols was observed concurrently with the consumption of membrane tocopherol and after tocopherol was exhausted the peroxidation of membrane lipids occurred. On the other hand, when radicals were initiated within the lipid region, the oxidation of thiols and the formation of thiobarbituric acid-reactive substances were suppressed to give an induction period until tocopherol fell below a critical level. Our results indicate that the surface thiols of extrinsic proteins may compete with alpha-tocopherol for trapping aqueous radicals and spare tocopherol to some extent, whereas the oxidation of intrinsic buried thiols may commence due to lipid-derived radicals produced after tocopherol was consumed. In conclusion, alpha-tocopherol in the membrane can break the free radical chain efficiently to inhibit the lipid peroxidation. However, the effect of tocopherol on the inhibition of membrane protein damage, exhibited by the loss of thiols and the formation of high-molecular-weight proteins, would be different depending on the site of initial radical generation.
Amidines↗
Inhibition of PGE2 production in macrophages from vitamin E-treated rats.
Rat peritoneal macrophages from vitamin E-treated rats (5 mg per rat for 6 successive days) contained 403.3 +/- 90.7 ng alpha-tocopherol/10(6) cells, whereas control macrophages contained 1.2 +/- 0.4 ng. PGE2 production in the macrophages from vitamin E-treated rats was significantly suppressed when stimulated with PMA and calcium ionophore A23187. The mechanism of vitamin E inhibition of PGE2 production in macrophages was investigated. The release of (14C)-arachidonic acid from pre-labeled macrophages and the conversion of (14C)-arachidonic acid to PGE2 by the homogenate of the cells were remarkably reduced. These results strongly suggested that the inhibition of PGE2 production by vitamin E results from the inhibition of the activities of both phospholipase A2 and cyclooxygenase.
Animals↗
Urinary and serum galactitol in galactosemic patients.
Serum and urinary galactitol levels were examined in two patients with classical galactosemia. Even under strict dietary therapy, galactitol levels were much higher than those of healthy controls. In a 6-day-old patient who had eaten large amounts of galactose before diagnosis, it took more than two weeks for urinary galactitol to decrease to the stable value. In an 8-year-old case, more than ten days were required for urinary galactitol to reach the base line level after a galactose load of 1.25 g/kg. In both patients, the urinary galactose levels decreased rapidly. After loading with a small amount of galactose (5 g, equivalent to 200 ml of milk) in the latter patient, higher levels of urinary and serum galactitol were maintained for a long time, as compared with galactose, but they returned to baseline level after 24 hours. From these results, we discussed the use of urinary galactitol as an index to check galactose intake.
Child↗
Susceptibility of neonatal lipoproteins to oxidative stress.
We compared peroxidizability of neonatal and adult lipoproteins exposed to oxidative stress initiated by an azo-compound. Oxygen uptake showed a two-phase pattern, with slow oxygen uptake in the first phase and faster uptake in the second phase. During the first phase, tocopherol was consumed progressively, inhibiting lipid peroxidation by scavenging peroxy radicals. After the tocopherol concentration fell below a critical level, extensive propagation of chain oxidative reactions produced the rapid oxygen uptake in the second phase. In the first phase of neonatal lipoprotein oxidation, a faster oxygen uptake was observed and the length of this phase was shorter than in adults. The oxygen uptake rate in the second phase was smaller in the neonatal lipoproteins. In other words, neonatal lipoproteins were more susceptible to oxidative stress than were adult ones when tocopherol remained in lipoproteins, but after tocopherol depletion the reverse was true. These results were consistent with the finding that in neonatal lipoproteins the tocopherol/lipid ratio was significantly lower (length of the inhibitory phase was closely correlated to the lipoprotein tocopherol content). In addition, the average number of active bisallylic hydrogen atoms, which are considered to determine the relative susceptibility of polyunsaturated fatty acids to oxidation, was significantly smaller (oxygen uptake rate in the second phase was closely correlated to the active bisallylic hydrogen number) in neonatal lipoproteins, and the ratio of active bisallylic hydrogen to tocopherol content (which closely correlated to oxygen uptake rate in the first phase) was also significantly lower compared with the adult ratio. Under physiologic conditions, an intensive oxidation of lipoproteins sufficient to cause lipoprotein tocopherol to fall below critical levels is unlikely to occur.(ABSTRACT TRUNCATED AT 250 WORDS)
Adult↗
Vitamin E and the peroxidizability of erythrocyte membranes in neonates.
We showed the increased susceptibility of neonatal biomembranes to oxidation by a kinetic analysis using an azo compound as a free-radical initiator and red blood cell (RBC) ghosts as a model membrane. When the RBC ghosts were oxidized, oxygen consumption was suppressed during the induction period in which membrane tocopherol was consumed at a constant rate, while increased oxygen uptake was observed after the tocopherol was exhausted. The total tocopherol content was similar in cord, maternal, and adult RBC ghosts, and there were no differences in the induction period (tinh) among the three types of ghosts. While the oxygen uptake rate during the induction period (Rinh) was similar in cord and adult ghosts, the rate in the subsequent phase (Rp) was considerably faster in the cord ghosts. Fatty acid analysis in the membrane lipids showed that the active bisallylic hydrogen (active H) content was greater in cord ghosts than in adult ghosts. The active H content closely correlated with the Rp, but did not with the Rinh. The kinetic chain length (KCL), i.e., the ratio of the rate of propagation to that of initiation, was calculated from Rp and tocopherol consumption rate and KCL values were higher in cord ghosts than in adult ghosts. The faster Rp and the higher KCL of the cord ghosts were attributable to a greater active H content rather than to the tocopherol content.
Adult↗
Superoxide generation in leukocytes and vitamin E.
Superoxide generation in polymorphonuclear cells (PMNs) can be detected through determination of chemiluminescence by stimulation with opsonized zymosan in association with the Cypridina luciferin analogue, 2 methyl-6-phenyl-3,7-dihydroimidazol[1,2-a]pyradin-3-one. Following the addition of vitamin E to cell suspensions, chemiluminescence was suppressed by a vitamin E concentration of more than 80 micrograms/10(9) cells. Superoxide production in PMNs was suppressed by both very low and very high levels of vitamin E (less than 2 micrograms/10(9) cells and more than 50 micrograms/10(9) cells, respectively). The high level of more than 50 micrograms/10(9) cells, which may be a dangerous level, was attained only by the intramuscular administration of 50 mg/kg/day for three days in rats. Young human adults (who received 600 mg/day for 3 months) or premature infants (who received 40 mg/kg/day for 8-14 days) developed PMN vitamin E concentrations not exceeding 30 micrograms/10(9) cells, and chemiluminescence was not affected. This indicates that oral administration of vitamin E does not impair PMN function, even in preterm infants. On the other hand, there was no enhancement of PMN function in premature infants and adults after vitamin E supplementation.
Administration, Oral↗