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Biomedical subjects

I Matsuda

Publications and source records attributed to I Matsuda.

At least 361 records · Page 20Linked to original sources

Study of bioavailability and pharmacokinetics of theophylline following administration of two sustained release dosage forms as assessed by salivary data: Part II.

Bioavailability and pharmacokinetics of theophylline following administration of a marketed sustained release tablet (Theo-Dur) and a newly designed sustained release tablet (E-0686) have been studied in fifteen healthy volunteers by measuring plasma and salivary concentrations. The theophylline level in saliva was 42.3 +/- 0.008 (s.e.m.) % of the plasma level and its correlation coefficient was 0.908. This observation suggests that salivary levels are considered to be a good indicator of the plasma concentration of theophylline. Interformulation variability in the saliva/plasma ratio was not significant in four occasions (p greater than 0.05). Thus, it was confirmed that the saliva/plasma ratio was nearly constant after administration of sustained release preparations of theophylline. Bioequivalency as to the extent of bioavailability of the two preparations was demonstrated by measurements of plasma and salivary levels. Compared to the theophylline levels in non-smokers, lower concentrations were observed in smokers at elimination phase by measurements of both the plasma and salivary levels, but shorter elimination half-life in smokers was indicated only in salivary data.

Adult↗

Influence of the type of feeding on the presence of PIVKA-II in infants.

PIVKA-II levels were studied by a highly sensitive immunological method in two groups of infants, breast-fed and bottle-fed, at the age of 4 days, 1 month, 2 months, and 3 months. PIVKA-II could be demonstrated in 9 infants after the age of 1 month when they were breast-fed. In none of the bottle-fed infants PIVKA-II was present during the same period. This significant difference can probably be explained by the lower vitamin K1 content of human milk compared to commercial formulas. The frequently occurring biochemical deficiency of vitamin K indicates the need of prophylactic administration of vitamin K to all newborns.

Biomarkers↗

Relationship between serum concentration and daily dose of dantrolene in cerebral palsy patients.

Serum concentration of dantrolene and its active metabolite, 5-hydroxydantrolene were determined in 27 cerebral palsy patients. Correlation coefficients between the oral dose of dantrolene and serum levels of dantrolene and its major metabolite, 5-hydroxydantrolene were rather small in cerebral palsy patients. The mean half-times of dantrolene and 5-hydroxydantrolene were 3.41 (n = 6) and 4.00 (n = 5) hours, respectively. These values were about a half of those reported earlier [Lietman et al., 1974; Meyler et al., 1979; Flewellen et al., 1983]. The poor correlation between serum level and dose may be due to the variation in an extent of oral dantrolene availability.

Adolescent↗

Rhizoxin, a macrocyclic lactone antibiotic, as a new antitumor agent against human and murine tumor cells and their vincristine-resistant sublines.

Rhizoxin, isolated from a plant pathogenic fungus which causes rice seedling blight, inhibits the mitosis of the tumor cells in a manner similar to that of Vinca alkaloids as revealed by morphological study and flow cytometry analysis. This new 16-membered macrocyclic lactone showed similar chemotherapeutic effects to those of vincristine against L1210 and P388 leukemia-bearing mice. The drug is also effective against B16 melanoma inoculated i.p. or s.c. Rhizoxin, in contrast to the ansamacrolide, maytansine, was effective against human and murine tumor cells resistant to vincristine and Adriamycin in vitro and in vivo. A maximum 60% increase in life span was obtained in mice inoculated with P388 leukemia resistant to vincristine. Rhizoxin showed greater cytotoxicity in cultured tumor cells than did vincristine. Rhizoxin seems to bear consideration for further development as a new chemotherapeutic agent.

Animals↗

[Effects of halothane on sensory evoked potentials].

Intraoperative monitoring of central nervous system functions is useful for safe neurosurgical operations. For such a purpose, some kinds of sensory evoked potentials play significant roles, but their reliability during general anesthesia have not yet been established. The authors conducted experimental and clinical studies to reveal effects of halothane, a most popular anesthetic, on sensory evoked potentials. Eight adult cats, weighing 2.8-4.0 kg, were induced to anesthesia with thiopental and ether, and after tracheostomy and venous cannulation, they were immobilized with succinylcholine and artificially ventilated with mixture of oxygen, nitrous oxide halothane. The concentration of halothane was increased up to 4.0% by 0.5% steps. The body temperature, systemic blood pressure and carbon dioxide concentrations in expires gas were monitored continuously, and maintained within normal ranges as much as possible. The hypotension induced by halothane was easily corrected by dopamine infusion initially, but later became difficult to be controlled as the halothane concentration increased. In each concentration, short latency somatosensory evoked potentials by median nerve stimulations (SL-SEP), and brain stem auditory evoked potentials (BAEP) were recorded. Active electrode was placed on the bregma, and reference electrodes were placed on a hindlimb for SL-SEP, on the tongue for BAEP recordings. Peak amplitudes of SL-SEP were gradually decreased and finally disappeared without apparent dose dependency. Relatively the peaks with longer latencies were more affected than those with shorter latency such as P1 and N1. In BAEP, decrement of the amplitude was apparent in the peaks with longer latencies with an obvious dose dependency.(ABSTRACT TRUNCATED AT 250 WORDS)

Anesthesia, General↗

Effect of vitamin K administration on acarboxy prothrombin (PIVKA-II) levels in newborns.

PIVKA-II (protein induced by vitamin K absence or antagonist-II) was measured in two groups of newborns, one group being given 5 mg vitamin K at birth and the other untreated. The untreated group had a significantly higher proportion of PIVKA-II positive babies at 3 and 5 days of age than did the treated group. When vitamin K was administered to newborn babies whose normotest levels were less than 30%, it was found that the higher the pre-treatment PIVKA-II levels the greater the response to vitamin K, as monitored by the normotest. Thus PIVKA-II levels might be more useful than a coagulation test, since the low activity of vitamin K dependent coagulation factors sometimes reflects not vitamin K deficiency but impaired production of these factors because of immaturity. The findings support the view that vitamin K given prophylactically at birth will help to prevent neonatal bleeding.

Administration, Oral↗

Apolipoprotein and lipid abnormalities in uremic children on hemodialysis.

Plasma lipids and six plasma apolipoproteins were studied in uremic children on hemodialysis. Significant increases in plasma triglyceride, apolipoproteins (Apo) C-II and C-III and decreases in total cholesterol, HDL-cholesterol, Apo A-I, Apo A-II and Apo B were found in uremic children. The levels of Apo C-I did not differ between uremic children and normal controls. The ratio of (Apo A-I + Apo A-II)/HDL-cholesterol was significantly increased. These results indicate that uremic children on hemodialysis have similar lipid and apolipoprotein abnormalities to those found in adults who may have a risk of cardiovascular disease.

Adolescent↗

Cholecystokinin antagonism by benzodiazepines in the contractile response of the isolated guinea-pig gallbladder.

Three benzodiazepines, chlordiazepoxide (CDP), diazepam (DZP) and medazepam (MZP), inhibited the contractile response of circular muscle strips from the isolated guinea-pig gallbladder to sulfated cholecystokinin octapeptide (CCK8) in the presence of atropine. The dose-response curves for CCK8 were shifted in parallel to the right by 10(-6) to 10(-5) M of the three benzodiazepines, although the maximum response to CCK8 was depressed by higher concentrations. Schild plot analysis of the antagonism gave pA2 values of 6.70 for CDP and 7.33 for DZP and slopes of the regression lines close to 1.0, suggesting that the antagonism was competitive in nature. The responses to acetylcholine, histamine and bradykinin were also depressed by 10(-5) M of DZP, but no parallel shift of their dose-response curves was observed. The non-specific inhibitory action of the benzodiazepines on these agonists was presumed to be due to the calcium antagonist-like action of the benzodiazepines. The antagonism between CCK8 and the benzodiazepines in the gallbladder was unaffected by GABA.

Acetylcholine↗

The infantile form of sialidosis type II associated with congenital adrenal hyperplasia: possible linkage between HLA and the neuraminidase deficiency gene.

The possible genetic linkage between HLA and neuraminidase deficiency was studied in a female patient with combined abnormalities of the infantile form of sialidosis type II and congenital adrenal hyperplasia caused by 21-hydroxylase deficiency, and six members of her family. Her parents were consanguineous. The patient has the homozygous HLA haplotypes, TS-1, Cw3, DRw9. Four of the tested family members, including a distant male relative with congenital adrenal hyperplasia, were heterozygous of this HLA complex, and the neuraminidase activities in their skin fibroblasts and/or lymphocytes showed values between those of the patient and controls (25-48%), suggesting a carrier state of sialidosis. This indicates that the neuraminidase deficiency gene, similar to the 21-hydroxylase deficiency gene, is closely linked to the HLA genotype and is located on chromosome 6.

Adrenal Hyperplasia, Congenital↗

Novel structure of the 5' end region of the human argininosuccinate synthetase gene.

The structure of the 5' end region of the human argininosuccinate synthetase (AS) gene was analyzed in detail. The 5' flanking region up to 350 nucleotides from the putative transcription initiation site is unusually G+C rich (80%). Three repeats of a CCGCCC sequence and one complementary GGGCGG sequence are present in this region. It contains no CCAAT box-like sequence, but does contain one typical TATA box and a 20 bases-long inverted repeat sequence that could form a stem and loop structure just upstream from the TATA box. An octanucleotide sequence, AGAAGTGA, found in the 5' flanking region of the AS gene is also commonly present in those regions of the two other human genes expressed mainly in the liver. These structural features of the AS gene indicate that it shares common structures with two completely different groups of genes, i.e. tissue-specific genes and housekeeping ones. Moreover, two enhancer core-like sequences, alternating purine-pyrimidines tracts and two independent Alu type highly repetitive sequences are apparent in the first intron of the AS gene.

Argininosuccinate Synthase↗

Effects of dietary zinc deficiency on hepatic ornithine carbamoyltransferase and alcohol dehydrogenase activities in rats.

Hepatic ornithine carbamoyltransferase (OCT) and alcohol dehydrogenase (ADH) activities were measured in six groups of rats: (A) fed a severe zinc-(Zn-) deficient diet (1.98 ppm) for 5 weeks; (B) pair-fed control for group (A); (C) fed a less severe Zn-deficient diet (6.10 ppm) for 5 weeks; (D) pair-fed control for group (C); (E) fed a Zn-supplemented control diet (90.4 ppm) for 5 weeks; and (F) first fed the severe Zn-deficient diet for 5 weeks and then replaced on the Zn-supplemented control diet until a body weight corresponding to the final weight of group (E) was obtained. Hepatic OCT was similar in all these six groups. On the contrary, hepatic ADH was significantly reduced in groups (A) and (C) and in each of the corresponding pair-fed groups, (B) and (D). No differences were found between groups (A) and (B) or between groups (C) and (D). In group (F), ADH activity improved to a level equivalent to that in group (E). The changes in ADH activities were accompanied by changes in the hepatic Zn content. Thus, it is clear that: (1) the hepatic Zn content may not be affected by the amount of Zn intake alone, but by the combination of Zn and food intake; and (2) ADH, and not OCT, reflected the hepatic Zn content.

Alcohol Dehydrogenase↗

Zinc status of untreated histidinemic children.

In order to study zinc status in histidinemia, serum and hair zinc concentrations were measured in 40 untreated children with histidinemia (age 2 months-5 years). In 20 children (greater than 2 years of age) zinc content and carbonic anhydrase activity of erythrocytes and urinary excretion of zinc were also studied. The amount of zinc excreted was elevated in histidinemic children and showed a positive correlation with the urinary histidine concentration (gamma = 0.57, p less than 0.005). The means of serum zinc concentration, erythrocyte zinc concentration, and erythrocyte carbonic anhydrase activity were all similar in the histidinemic and the control children. Hair zinc concentration of histidinemic children was compared with that of controls of five different age groups: less than 5 months, 5-18 months, 18 months-2 years, 2-4 years, and 4-5 years. In all of these age groups, hair zinc content was similar. The incidence of low-hair-zinc level (less than 80 micrograms/g) in histidinemic children greater than 5 months of age (9 of 34) was significantly higher than in controls (18 of 180, p less than 0.05). The observation suggested the possibility that untreated histidinemia may cause chronic mild zinc deficiency in some histidinemic children.

Ammonia-Lyases↗

Clinicopathological correlation of IgA nephropathy in children.

22 patients with IgA nephropathy aged 7-16 years, 15 of whom were found by mass urine screening of school children, were divided into three groups based on the degree of their proteinuria at admission: group A (n = 6) below 0.5 g/day of urine protein, group B (n = 7) between 0.6 and 3.0, and group C (n = 9) above 3.0 g/day of urine protein. The degree of proteinuria seemed to be related to the severity of pathological changes of the glomerular basement membrane; most severe in group C, moderate in group B, and minimal in group A. IgA deposits in the mesangial area were found in all groups of patients, but those in the capillary walls were most frequently found in group C. In addition to electron-dense deposits in the mesangial area, which was found in all groups of patients, the subendothelial and subepithelial deposits were the most remarkable changes found in group C. During the clinical observation period, which was between 2.0 and 7.1 years, no patient belonging to group A progressed to groups B or C. 4 cases in group C developed chronic renal failure, but none in the other groups did. The amount of urine protein might be used as a valuable parameter of the pathological damage of the glomerulus in children with IgA nephropathy.

Adolescent↗